Methods and compositions for treating cardiovascular disease using 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 26156, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 molecules

ABSTRACT

The present invention relates to methods for the diagnosis and treatment of cardiovascular disease, including, but not limited to, atherosclerosis, reperfusion injury, hypertension, restenosis, arterial inflammation, heart failure, thrombosis and endothelial cell disorders. Specifically, the present invention identifies the differential expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 and 6585 genes in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. The present invention describes methods for the diagnostic evaluation and prognosis of various cardiovascular diseases, and for the identification of subjects exhibiting a predisposition to such conditions. The invention also provides methods for identifying a compound capable of modulating cardiovascular disease. The present invention also provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.

RELATED APPLICATIONS

[0001] The present application claims the benefit of U.S. Provisional Application serial No. 60/353,224, filed on Feb. 1, 2002, of U.S. Provisional Application serial No. 60/364,529, filed on Mar. 15, 2002, of U.S. Provisional Application serial No. 60/373,861, filed on Apr. 19, 2002, of U.S. Provisional Application serial No. 60/376,287, filed on Apr. 29, 2002, of U.S. Provisional Application serial No. 60/388,080, filed on Jun. 12, 2002, of U.S. Provisional Application serial No. 60/390,971, filed on Jun. 24, 2002, of U.S. Provisional Application serial No. 60/394,130, filed on Jul. 3, 2002, of U.S. Provisional Application serial No. 60/394,797 filed on Jul. 10, 2002, of U.S. Provisional Application serial No. 60/404,904, filed on Aug. 21, 2002, of U.S. Provisional Application serial No. 60/405,450, filed on Aug. 23, 2002, of U.S. Provisional Application serial No. 60/408,070, filed on Sep. 4, 2002, of U.S. Provisional Application serial No. 60/424,300, filed on Nov. 6, 2002, of U.S. Provisional Application serial No. 60/431,079, filed on Dec. 5, 2002, and of U.S. Provisional Application serial No. 60/431,042, filed on Dec. 5, 2002. The entire contents of these provisional patent applications are hereby incorporated by this reference.

BACKGROUND OF THE INVENTION

[0002] Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack, stroke, and peripheral vascular disease resulting in significant disability and limb loss, and thereby the principle cause of death in the United States.

[0003] Atherosclerosis is a complex disease involving aspects of lipid metabolism and vascular inflammation. Both have significant effects on the initiation and progression of atherosclerosis. Irregular lipid metabolism is a very well established risk factor for atherosclerosis. Elevated low density lipoprotein (LDL), very low density lipoproteins (VLDL), triglycerides and low levels of high density lipoproteins (HDL) all independently contribute to atherosclerosis development and/or progression. There are a number of effective therapies currently being utilized in the clinic that result in lowering of these risk factors and, in turn decrease the rate of mortality and morbidity associated with atherosclerotic disease. Some of these therapies include the cholesterol lowering drugs statins, the triglyceride lowering drugs fibrates and niacin and the triglyceride lowering/HDL raising PPAR alpha activators. There is a need to identify new targets for atherosclerosis therapy.

[0004] There have been significant advances made in understanding the role that inflammation plays in the process of atherosclerosis. Atherosclerosis involves many cell types and molecular factors (described in, for example, Ross (1993) Nature 362: 801-809). The process, in normal circumstances a protective response to insults to the endothelium and smooth muscle cells (SMCs) of the wall of the artery, consists of the formation of fibrofatty and fibrous lesions or plaques, preceded and accompanied by inflammation. The advanced lesions of atherosclerosis may occlude the artery concerned, and result from an excessive inflammatory-fibroproliferative response to numerous different forms of insult. Injury or dysfunction of the vascular endothelium is a common feature of many conditions that predispose an individual to accelerated development of atherosclerotic cardiovascular disease. There has been considerable effort in establishing that hypertension contributes to atherosclerosis. The identification of molecules that regulate blood pressure and vascular tone will be useful in discovering new therapies to treat cardiovascular diseases such as atherosclerosis.

DETAILED DESCRIPTION OF THE INVENTION

[0005] The present invention provides methods and compositions for the diagnosis and treatment of cardiovascular disease. As used herein, disorders involving the heart, or “cardiovascular disease” or a “cardiovascular disorder” include a disease or disorder which affects the cardiovascular system, e.g., the heart, the blood vessels, and/or the blood. A cardiovascular disorder can be caused by an imbalance in arterial pressure, a malfunction of the heart, or an occlusion of a blood vessel, e.g., by a thrombus. A cardiovascular disorder includes, but is not limited to disorders such as arteriosclerosis, atherosclerosis, cardiac hypertrophy, ischemia reperfusion injury, restenosis, arterial inflammation, vascular wall remodeling, ventricular remodeling, rapid ventricular pacing, coronary microembolism, tachycardia, bradycardia, pressure overload, aortic bending, coronary artery ligation, vascular heart disease, valvular disease, including but not limited to, valvular degeneration caused by calcification, rheumatic heart disease, endocarditis, or complications of artificial valves; atrial fibrillation, long-QT syndrome, congestive heart failure, sinus node dysfunction, angina, heart failure, hypertension, atrial fibrillation, atrial flutter, pericardial disease, including but not limited to, pericardial effusion and pericarditis; cardiomyopathies, e.g., dilated cardiomyopathy or idiopathic cardiomyopathy, myocardial infarction, coronary artery disease, coronary artery spasm, ischemic disease, arrhythmia, sudden cardiac death, and cardiovascular developmental disorders (e.g., arteriovenous malformations, arteriovenous fistulae, raynaud's syndrome, neurogenic thoracic outlet syndrome, causalgia/reflex sympathetic dystrophy, hemangioma, aneurysm, cavernous angioma, aortic valve stenosis, atrial septal defects, atrioventricular canal, coarctation of the aorta, ebsteins anomaly, hypoplastic left heart syndrome, interruption of the aortic arch, mitral valve prolapse, ductus arteriosus, patent foramen ovale, partial anomalous pulmonary venous return, pulmonary atresia with ventricular septal defect, pulmonary atresia without ventricular septal defect, persistance of the fetal circulation, pulmonary valve stenosis, single ventricle, total anomalous pulmonary venous return, transposition of the great vessels, tricuspid atresia, truncus arteriosus, ventricular septal defects). A cardiovascular disease or disorder also can include an endothelial cell disorder.

[0006] As used herein, an “endothelial cell disorder” includes a disorder characterized by aberrant, unregulated, or unwanted endothelial cell activity, e.g., proliferation, migration, angiogenesis, or vascularization; or aberrant expression of cell surface adhesion molecules or genes associated with angiogenesis, e.g., TIE-2, FLT and FLK. Endothelial cell disorders include tumorigenesis, tumor metastasis, psoriasis, diabetic retinopathy, endometriosis, Grave's disease, ischemic disease (e.g., atherosclerosis), and chronic inflammatory diseases (e.g., rheumatoid arthritis).

[0007] A cardiovascular disease can also include thrombosis. Thrombosis can result from platelet dysfunction, e.g. seen in myocardial infarction, angina, hypertension, lipid disorders, diabetes mellitus; myelodysplastic syndromes; myeloproliferative yndromes (including polycythermia vera and thombocythemia); thrombotic thrombocytopenic purpuras; HIV-induced platelet disorders (AIDS-Thrombocytopenia); heparin induced thrombocytopenia; mural cell alterations/interactions leading to platelet aggregation/degranulation, vascular endothelial cell activation/injury, monocyte/macrophage extravasation and smooth muscle cell proliferation; autoimmune disorders such as, but not limited to vasculitis, antiphospholipid syndromes, systemic lupus erythromatosis; inflammatory diseases, such as, but not limited to immune activation; graft Vs host disease; radiation induced hypercoagulation; clotting factor dysregulation either hereditary (autosomal dominant or recessive) such as, but not limited to clotting factor pathways including protein C/S, Anti-thrombin III deficiency, and the Factor V Leiden mutation or acquired such as but not limited to autoimmune, cancer-associated and drug-induced dysregulation of clotting factors.

[0008] “Treatment”, as used herein, is defined as the application or administration of a therapeutic agent to a patient, or application or administration of a therapeutic agent to an isolated tissue or cell line from a patient, who has a disease or disorder, a symptom of disease or disorder or a predisposition toward a disease or disorder, with the purpose of curing, healing, alleviating, relieving, altering, remedying, ameliorating, improving or affecting the disease or disorder, at least one symptom of disease or disorder or the predisposition toward a disease or disorder. A therapeutic agent includes, but is not limited to, small molecules, peptides, antibodies, ribozymes and antisense oligonucleotides. Representative molecules are described herein.

[0009] The present invention is based, at least in part, on the discovery that nucleic acid and protein molecules, (described infra), are differentially expressed in cardiovascular disease states relative to their expression in normal, or non-cardiovascular disease states. The modulators of the molecules of the present invention, identified according to the methods of the invention can be used to modulate (e.g., inhibit, treat, or prevent) or diagnose cardiovascular disease, including, but not limited to, atherosclerosis and thrombosis.

[0010] “Differential expression”, as used herein, includes both quantitative as well as qualitative differences in the temporal and/or tissue expression pattern of a gene. Thus, a differentially expressed gene may have its expression activated or inactivated in normal versus cardiovascular disease conditions (for example, in an experimental cardiovascular disease system such as in an animal model for atherosclerosis). The degree to which expression differs in normal versus cardiovascular disease or control versus experimental states need only be large enough to be visualized via standard characterization techniques, e.g., quantitative PCR, Northern analysis, subtractive hybridization. The expression pattern of a differentially expressed gene may be used as part of a prognostic or diagnostic cardiovascular disease, e.g., artheroscierosis and/or thrombosis, evaluation, or may be used in methods for identifying compounds useful for the treatment of cardiovascular disease, e.g., atherosclerosis and/or thrombosis. In addition, a differentially expressed gene involved in cardiovascular disease may represent a target gene such that modulation of the level of target gene expression or of target gene product activity will act to cure, heal, alleviate, relieve, alter, remedy, ameliorate, improve or affect a cardiovascular disease condition, e.g., atherosclerosis and/or thrombosis. Compounds that modulate target gene expression or activity of the target gene product can be used in the treatment of cardiovascular disease. Although the genes described herein may be differentially expressed with respect to cardiovascular disease, and/or their products may interact with gene products important to cardiovascular disease, the genes may also be involved in mechanisms important to additional cardiovascular cell processes.

[0011] Molecules of the Present Invention

[0012] Gene ID 1682

[0013] The human 1682 sequence (SEQ ID NO:1), (GI:340010), known also as human dual specificity protein kinase (TTK or PYT), is approximately 3866 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 1026 to 3551 of SEQ ID NO:1, encodes a 841 amino acid protein (SEQ ID NO: 2) (GI:340011).

[0014] As assessed by TaqMan analysis, 1682 mRNA expression was detected in megakaryocytic and erythroid lineages in vitro and in bone marrow megakaryocytes (CD41+ cells). Little or no 1682 mRNA expression was observed in the major human organs, i.e., heart, lung, liver, kidney and spleen. Higher levels of 1682 mRNA was observed in the platelets of patients with acute coronary syndromes (myocardial infarct and unstable angina) that also have a history of diabetes as compared with platelets from patients with no history of diabetes and also with normal, age-matched, volunteers.

[0015] Signal transduction via serine/threonine and/or tyrosine kinases has been implicated in platelet reactivity, a key component of thrombosis associated with acute coronary syndromes [Circulation. 2000. 102(16):1924-1930]. Evidence exists suggesting that the platelets of diabetic patients are more reactive than normal platelets [Thrombosis Research. 1998. 90(4): 181-90]. 1682 is stimulated by the cytokine tumor necrosis factor (TNF) [Cytokine. 2000. 12(2): 142-150], and elevated serum TNF levels occur in patients with diabetes. Collectively, these data indicate that the increased TNF levels in diabetic patients stimulate increased 1682 expression, thereby contributing to the platelet reactivity and the acute coronary syndrome. Due to these observations and the expression pattern of 1682 in megakaryocytic and erythroid lineages in vitro, modulators of 1682 activity would block platelet reactivity and thus be useful as therapeutics in treating thrombosis and thrombotic conditions. 1682 polypeptides of the present invention are useful to screen for modulators of 1682 activity

[0016] Gene ID 6169

[0017] The human 6169 sequence (SEQ ID NO:3), (GI:1930074), known also as C-4 methyl sterol oxidase (DESP4), is approximately 1751 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 27 to 908 of SEQ ID NO:3, encodes a 293 amino acid protein (SEQ ID NO: 4) (GI:1930075).

[0018] As assessed by TaqMan analysis, 6169 mRNA was expressed at high levels in human liver, as compared to other human tissues tested. 6169 mRNA was regulated by cholestyramine in a marmoset model of atherosclerosis. 6169 mRNA was repressed by n-3 polyunsaturated fatty acid in an African Green Monkey model of atherosclerosis.

[0019] 6169 (C-4 methyl sterol oxidase) is the human ortholog of the yeast gene ERG25 which has been implicated in sterol biosynthesis. Inhibition of C-4 methyl sterol oxidase is predicted to reduce total cholesterol and triglycerides. 6169 mRNA expression was repressed by n-3 polyunsaturated (hypolipidemic diet) and also regulated by cholestyramine and exhibits liver enriched expression. Due to the regulation pattern of 6169 marmoset and African green monkey model atherosclerosis, modulators of 6169 activity would be useful in treating cardiovascular diseases including but not limited to atherosclerosis and hypercholesterolemia. 6169 polypeptides are useful in screening for modulators of 6169 activity.

[0020] Gene ID 6193

[0021] The human 6193 sequence (SEQ ID NO:5), also known as a GPCR, is approximately 1029 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 1 to 1029 of SEQ ID NO:5, encodes a 342 amino acid protein (SEQ ID NO: 6).

[0022] As assessed by TaqMan analysis, 6193 mRNA was expressed in human blood vessels and in vessel-rich organs, the highest expression level seen in skeletal muscle. 6193 mRNA expression was also seen in the vasculature in both endothelial and smooth muscle cells. 1

[0023] Due to the widespread expression of 6193 in human vasculature, modulators of 6193 activity would modulate vascular tone and thus would be useful in treating cardiovascular disorders, including but not limited to hypertension and those conditions characterized by hypertension. 6193 polypeptides would be useful in screening for modulators of 6193 activity.

[0024] Gene ID 7771

[0025] The human 7771 sequence (SEQ ID NO:7), (GI:468325), known also as a human phospholipid transfer protein, is approximately 1750 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 88 to 1569 of SEQ ID NO:7, encodes a 493 amino acid protein (SEQ ID NO: 8) (GI:468326).

[0026] As assessed by TaqMan analysis, 7771 mRNA expression was detected in brain, heart, spleen, placenta, and erythroid and megakaryocytic lineages in vitro. 7771 mRNA was also expressed at highest levels in brain and CD61+ bone marrow megakaryocytes. 7771 mRNA was also detected in platelets from patients with coronary artery disease and at lower levels in platelets from normal volunteers.

[0027] 7771 protein modulates high density lipoprotein (HDL) particles, converting HDL into larger and smaller particles. Lipoproteins play a critical role in maintaining the phospholipid membrane of platelets and the vessel wall. Lipoproteins are also implicated in maintaining hemostasis and preventing thrombosis. The increased reactivity of platelets from patients with acute coronary diseases results from increased expression of genes such as 7771. Therefore, due to the expression pattern of 7771 in the erythroid and megakaryocytic lineages in vitro and its role in vivo, modulators of 7771 activity would be useful in reducing increased reactivity in the platelets of patients with acute coronary diseases. 7771 polypeptides of the present invention are useful to screen for modulators of 7771 activity.

[0028] Gene ID 14395

[0029] The human 14395 sequence (SEQ ID NO:9), (GI: 10946200), known also as human neuromedin receptor 1 (NMUR1), is approximately 1212 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 1 to 1212 of SEQ ID NO:9, encodes a 403 amino acid protein (SEQ ID NO: 10) (GI:10946201).

[0030] As assessed by TaqMan analysis, 14395 mRNA showed restricted exresssion in an organ recital study. The highest expression of 14395 mRNA was observed in breast, adipose, and pancreas. Medium expression of 14395 mRNA was shown in blood vessels, kidney, liver and prostate. Among cardiovascular rich organs (heart, kidney, skeletal muscle and liver), 14395 mRNA was expressed in kidney and liver. There is little or no expression in heart and skeletal muscle. 14395 mRNA was also expressed in all veins and some aorta/arteries. In addition, 14395 mRNA was expressed in laser captured vascular smooth muscle cells in vein.

[0031] Due to the widespread expression of 14395 in human vasculature and kidney, modulators of 14395 activity would modulate vascular tone and thus would be useful in treating cardiovascular disorders, including but not limited to hypertension and those conditions characterized by hypertension. 14395 polypeptides would be useful in screening for modulators of 14395 activity.

[0032] Gene ID 29002

[0033] The human 29002 sequence (SEQ ID NO: 11), known also as a eukaryotic protein kinase, is approximately 2370 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 43 to 1338 of SEQ ID NO:11, encodes a 431 amino acid protein (SEQ ID NO: 12).

[0034] As assessed by TaqMan analysis, 29002 mRNA was expressed in both in vivo and in vitro samples. 29002 mRNA was expressed in human vasculature. Expression of 29002 mRNA was upregulared in primate atheroma samples compared to normal vessels. In addition, 29002 mRNA was upregulated in macrophages which had been stimulated with CD40 ligand, but not in endothelial cells or smooth muscle cells. In contrast, 29002 mRNA was down-regulated in endothelial cells that were stimulated with mevastatin.

[0035] Due to the expression pattern of 29002 in the human vasculature, modulation of 29002 would affect atherognesis and thus be useful as treatment for atherogenesis and atherogenic events. 29002 polypeptides are useful in screening for modulators of 29002 activity.

[0036] Gene ID 33216

[0037] The human 33216 sequence (SEQ ID NO:13), (GI:4768276), known also as a human long-chain acyl-CoA synthetase or fatty acid transport protein 5 (FATP-5), is approximately 2347 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 71 to 2143 of SEQ ID NO:13, encodes a 690 amino acid protein (SEQ ID NO: 14) (GI:4768277).

[0038] As assessed by TaqMan analysis 33216 mRNA was expressed in human liver. Expression of 33216 mRNA in the liver was regulated by statin, in vivo model of African Green Monkey, PPAR alpha agonist (a human hepatocyte model), and regulated by a high cholesterol diet in vivo (African Green Monkey model).

[0039] 33216 (FATP-5) is a member of a family of the Fatty Acid Transport Proteins that has been implicated in lipid metabolism. Inhibition of 33216 is predicted to reduce total cholesterol and triglycerides. Therefore, due to 33216 expression patten in various animal models and its functional role in vivo, modulaotrs of 33216 activity would be useful in treating cardiovascular disorders, including but not limited to atherosclerosis. 33216 polypeptides would be useful in screening for modulators of 33216 activity.

[0040] Gene ID 43726

[0041] The human 43726 sequence (SEQ ID NO: 15), (GI:3176926), known also as galanin 2 receptor homolog, is approximately 1157 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 26 to 1132 of SEQ ID NO:15 encodes a 368 amino acid protein (SEQ ID NO:16) (GI:3176927).

[0042] As assessed by TaqMan analysis, 43726 mRNA was expressed in human brain, in megakaryocytic and erythroid lineages in vitro and in bone marrow megakaryocytes (CD61+ cells). 43726 mRNA was also detected in platelets from patients with coronary artery disease but not in platelets from normal volunteers.

[0043] Galinin is a neuropeptide that regulates several neural functions including nociception and cognition through ligation with 3 known receptors, galinin receptors 1-3. The mechanism by which the Gal-3 receptor functions is not known, but evidence suggests a role for galinin and galinin receptors in the regulation of neurotrasmitter release [Journal of Biological Chemistry 1998. 273(36):23321-23326]. Due to the expression of 43726 in platelets, and its functional role as the human galanin-3 receptor, it constitutes a parallel pathway may in platelets, implicating 43726 in the control of platelet secretory granule release (degranulation), an important step in thrombus formation. Therefore, modulators of 43726 activity are useful as therapeutics in treating thrombosis and thrombotic conditions. 43726 polypeptides are useful in screening for modulators of 43726 activity.

[0044] Gene ID 69292

[0045] The human 69292 sequence (SEQ ID NO: 17), (GI: 10334989), known also as potassium-dependent Na/Ca exchanger (NCKX3), is approximately 3763 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 38 to 1972 of SEQ ID NO:17, encodes a 644 amino acid protein (SEQ ID NO:18) (GI:14717396).

[0046] 69292 mRNA was detected by TaqMan analysis in human brain, megakaryocyte precursors (CD34+ cells), in megakaryocytes generated in vitro and in CD41+ bone marrow megakaryocytes. 69292 mRNA was found to be present in platelets, with a relative expression higher in platelets from patients with unstable angina and myocardial infraction as compared with platelets from patients with stable angina and normal volunteers.

[0047] Calcium mobilization is a critical component of platelet activation and degranulation. Potassium dependent sodium/calcium exchange activity has been previously demonstrated in platelets [J. Gen. Physiol. 1999. 114:701-711.]. Due to 69292 expression in human brain, megakaryocyte precursors (CD34+ cells), in megakaryocytes generated in vitro and in CD41+ bone marrow megakaryocytes and its funcitional roles as a sodium/calcium exchanger, 69292 is able to regulate intracellular calcium levels in platelets, thereby regulating platelet reactivity. Modulators of 69292 activity would function to regulate platelet activity and would be useful in treating thrombosis and thrombotic conditions. 69292 polypeptides are useful in screening for modulators of 69292 activity.

[0048] Gene ID 26156

[0049] The human 26156 sequence (SEQ ID NO:19), is approximately 1228 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 78 to 728 of SEQ ID NO: 19, encodes a 216 amino acid protein (SEQ ID NO:20).

[0050] As assessed by TaqMan analysis, 26156 mRNA was expressed in artery and vein samples. Modulators of 26156 activity are useful in treating cardiovascular diseases. 26156 polypeptides of the present invention are useful in screening for modulators of 26156 activity.

[0051] Gene ID 32427

[0052] The human 32427 sequence (SEQ ID NO:21), also known as Acyl co A synthase 5 (ACS 5), is approximately 3371 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 114 to 2333 of SEQ ID NO:21, encodes a 739 amino acid protein (SEQ ID NO:22).

[0053] As assessed by TaqMan analysis, 32427 mRNA was expressed in the human liver. 32427 mRNA was shown to be repressed by cholesterol in monkey liver model. 32427 mRNA was also shown to be up-regulated in human hepatocytes by combination statin/PPAR alpha agonist treatment.

[0054] 32427 is also known as Acyl co A synthase 5 (ACS 5). Inhibition of 32427 or ACS 5 is predicted to reduce total cholesterol and triglycerides. 32427 is repressed by cholesterol and elevated by the hypolipidemic therapeutic combination of statin/fibrate. This pattern is identical to that observed for genes know to be involved in cholesterol metabolism. Therefore, 32427 has a potential role in cholesterol metabolism/biosynthesis. Due to the 32427 expression in the human liver and various animal models, modulators of 32427 activity are useful in treating cardiovascular diseases. 32427 polypeptides of the present invention are useful in screening for modulators of 32427 activity.

[0055] Gene ID 2402

[0056] The human 2402 sequence (SEQ ID NO:23), known also as EDG-4 GPCR, is approximately 1734 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 85 to 1233 of SEQ ID NO:23, encodes a 382 amino acid protein (SEQ ID NO:24).

[0057] As assessed by TaqMan analysis, 2402 mRNA was expressed in the human liver. 2402 mRNA was also repressed by cerivastatin a marmoset model. In a human hepatocyte model, 2402 mRNA was also regulated by statin/PPAR alpha agonist in vitro.

[0058] 2402 is also known as EDG-4 GPCR. Regulation of 2402 or EDG-4 is predicted to reduce total cholesterol and triglycerides. 2402 expression is repressed by cerivastatin in a marmoset model which predicts a role in cholesterol metabolism/biosynthesis. Due to 2402 mRNA expression in the human liver and marmoset model, modulators of 2402 activity are useful in treating cardiovascular diseases. 2402 polypeptides of the present invention are useful in screening for modulators of 2402 activity.

[0059] Gene ID 7747

[0060] The human 7747 sequence (SEQ ID NO:25), known also as GMP reductase, is approximately 277 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 174 to 260 of SEQ ID NO:25, encodes a 29 amino acid protein (SEQ ID NO: 26).

[0061] As assessed by TaqMan analysis, 7747 mRNA was expressed in the human liver. 7747 mRNA was also repressed by cerivastatin a marmoset model.

[0062] 7747 is known also as GMP reductase. Regulation of 7747 or GMP reductase is predicted to reduce total cholesterol and triglycerides. 7747 expression is repressed by cerivastatin in a marmoset model which predicts a role in cholesterol metabolism/biosynthesis. Due to 7747 mRNA expression in the human liver and marmoset model, modulators of 7747 activity are useful in treating cardiovascular diseases. 7747 polypeptides of the present invention are useful in screening for modulators of 7747 activity.

[0063] Gene ID 1720

[0064] The human 1720 sequence (SEQ ID NO:27), known also as ZAP70 kinase, is approximately 3151 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 286 to 2145 of SEQ ID NO:27, encodes a 619 amino acid protein (SEQ ID NO: 28).

[0065] As assessed by TaqMan expression, 1720 mRNA was expressed in the human liver. 1720 mRNA was also shown to be repressed by fenofibrate in vivo and by PPAR alpha selective agonist in vivo.

[0066] 1720 is also known as ZAP70 kinase. Inhibition of 1720 or ZAP70 kinase is predicted to reduce total cholesterol and triglycerides. 1720 expression is repressed by fenofibrate and a PPAR alpha selective agonist in a marmoset model which predicts a role in triglyceride/cholesterol metabolism. Due to 1720 mRNA expression in the human liver and marmoset model, modulators of 1720 activity are useful in treating cardiovascular diseases. 1720 polypeptides of the present invention are useful in screening for modulators of 1720 activity.

[0067] Gene ID 9151

[0068] The human 9151 sequence (SEQ ID NO:29), known also as sorbitol dehydrogenase, is approximately 1808 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 142 to 1215 of SEQ ID NO:29, encodes a 357 amino acid protein (SEQ ID NO:30).

[0069] As assessed by TaqMan analysis, 9151 mRNA was expression in human liver. 9151 mRNA expression was shown to be repressed by statin therapy in vivo, fenofibrate in vivo and PPAR alpha selective agonist in vivo

[0070] 9151 is also known as sorbitol dehydrogenase. Inhibition of 9151 or sorbitol dehydrogenase is predicted protect against the development of atherosclerosis. 9151 mRNA expression is independently repressed by statin, fenofibrate and a PPAR alpha selective agonist in a marmoset model which predicts a role in triglyceride/cholesterol metabolism. Due to 9151 mRNA expression in the human liver and various animal models, modulators of 9151 activity are useful in treating cardiovascular diseases. 9151 polypeptides of the present invention are useful in screening for modulators of 9151 activity.

[0071] Gene ID 60491

[0072] The human 60491 sequence (SEQ ID NO:31), known also as a novel glycerol phosphate acytransferase (GPAT), is approximately 2682 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 121 to 2448 of SEQ ID NO:31, encodes a 775 amino acid protein (SEQ ID NO: 32).

[0073] As assessed by TaqMan analysis, 60491 mRNA was expressed in the human liver. 60491 mRNA expression was also repressed by statin therapy and by fenofibrate in vivo.

[0074] 60491 is also known as a novel glycerol phosphate acytransferase (GPAT). Inhibition of 60491, which represents a novel Glycerol Phosphate Acyltransferase (GPAT), is predicted to lower triglyceride and/or cholesterol levels. GPAT's are a class of enzymes that have a demonstrated role in triglyceride metabolism. 60491 mRNA expression is independently repressed by statin, and fenofibrate in a marmoset model, which supports a role in triglyceride/cholesterol metabolism for this gene. Due to 60491 mRNA expression in the human liver and various animal models, modulators of 60491 activity are useful in treating cardiovascular diseases. 60491 polypeptides of the present invention are useful in screening for modulators of 60491 activity.

[0075] Gene ID 1371

[0076] The human 1371 sequence (SEQ ID NO:33), known also as tyrosine kinase BMX, is approximately 2604 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 119 to 2212 of SEQ ID NO:33, encodes a 697 amino acid protein (SEQ ID NO: 34).

[0077] As assessed by Taqman analysis, 1371 mRNA was expressed in human vessels and endothelial cells. 1371 mRNA was also shown to be expressed in endothelial cells regulated by PPAR alpha agonist (cardioprotective).

[0078] 1371 is also known as tyrosine kinase BMX. Inhibition of 1371 or BMX kinase is predicted to protect against the development of atherosclerosis. 1371 gene expression is repressed by a PPAR alpha selective agonist in endothelial cells in vitro and 1371 is highly expressed in human arteries (normal and disease), supporting a potential role in the development of atherosclerotic lesions. Due to 1371 mRNA expression in human vessels and endothelial cells, modulators of 1371 activity are useful in treating cardiovascular diseases. 1371 polypeptides of the present invention are useful in screening for modulators of 1371 activity.

[0079] Gene ID 7077

[0080] The human 7077 sequence (SEQ ID NO:35), known also as a putative kinase, is approximately 6629 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 1 to 6416 of SEQ ID NO:35, encodes a 2080 amino acid protein (SEQ ID NO: 36).

[0081] As assessed by Taqman analysis, 7077 mRNA was expressed in human vessels and endothelial cells. 7077 mRNA was also shown to be expressed in endothelial cells regulated by PPAR alpha agonist (cardioprotective).

[0082] Inhibition of 7077 is predicted to protect against the development of atherosclerosis. 7077 gene expression is repressed by a PPAR alpha selective agonist in endothelial cells in vitro and 7077 is highly expressed in human arteries (normal and disease), supporting a potential role in the development of atherosclerotic lesions. Due to 7077 mRNA expression in human vessels and endothelial cells, modulators of 7077 activity are useful in treating cardiovascular diseases. 7077 polypeptides of the present invention are useful in screening for modulators of 7077 activity.

[0083] Gene ID 33207

[0084] The human 33207 sequence (SEQ ID NO:37), known also as a putative novel acyltransferase, is approximately 1945 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 69 to 1802 of SEQ ID NO:37, encodes a 577 amino acid protein (SEQ ID NO:38).

[0085] 33207 gene expression was independently repressed by cerivastatin, fenofibrate and a PPAR alpha selective agonist in a marmoset model.

[0086] 33207 is also known as a putative novel acyltransferase. Inhibition of 33207 is predicted to reduce total cholesterol and triglycerides. 33207 gene expression is independently repressed by cerivastatin, fenofibrate and a PPAR alpha selective agonist in a marmoset model which predicts a role in triglyceride/cholesterol metabolism. Due to 33207 mRNA expression in various animal models, modulators of 33207 activity are useful in treating cardiovascular diseases. 33207 polypeptides of the present invention are useful in screening for modulators of 33207 activity.

[0087] Gene ID 1419

[0088] The human 1419 sequence (SEQ ID NO:39), known also as ephrin receptor, is approximately 3903 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 712 to 3825 of SEQ ID NO:39, encodes a 1037 amino acid protein (SEQ ID NO:40).

[0089] As assessed by TaqMan analysis, 1419 mRNA was expressed in smooth muscle, vessel and vein.

[0090] 1419 is also known as an Ephrin receptor. Inhibition of 1419 is predicted to have beneficial effects in vascular tone/hypertension. 1419 exhibits restricted expression in human smooth muscle cells and human vessel. The expression of 1419 coupled with a potential link to the Rho kinase pathway, known to be involved in vasoactivity, predicts a role for 1419 in vascular tone disease. Due to 1419 mRNA expression in smooth muscle, vessel and vein, modulators of 1419 activity are useful in treating cardiovascular diseases. 1419 polypeptides of the present invention are useful in screening for modulators of 1419 activity.

[0091] Gene ID 18036

[0092] The human 18036 sequence (SEQ ID NO:41), known also as a calpain 10 protease, is approximately 2180 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 183 to 1736 of SEQ ID NO:41, encodes a 517 amino acid protein (SEQ ID NO:42).

[0093] As determined by TaqMan analysis, 18036 mRNA expression was shown to be upregulated in the brain, kidney and heart. 18036 mRNA was also found to be upregulated in congestive heart failure (CHF) human tissue samples.

[0094] Calpains are cysteine proteases that combine thiol protease activity with calmodulin-like activity. Inhibiting calpain activity leads to attenuated hypoxia-induced cell injury. Increased preload, as seen in pathophysiological states such as heart failure, also induces troponin I degradation independently of myocardial ischemia. Troponin I degradation is a reported marker of myocardial injury in ischemic cornonary syndromes. Due to 18036 mRNA expression in the brain, kindney and heart, along with its functional role, modulators of 18036 activity would be useful in treating disorders associated with cardiovascular disease. 18036 polypeptides of the present invention are useful in screening for modulators of 18036 activity.

[0095] Gene ID 16105

[0096] The human 16105 sequence (SEQ ID NO:43), known also as a Protein Serine/Threonine Phosphatase family member (PP2C homolog), is approximately 1676 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 391 to 1449 of SEQ ID NO:43, encodes a 352 amino acid protein (SEQ ID NO:44).

[0097] As determined by TaqMan analysis, 16105 mRNA expression was upregulated in heart and brain. Further TaqMan experiments indicated that 16105 was also upregulated in human congestive heart failure tissue and hypertrophied myocytes compared to the normal tissue. In addition, 16105 mRNA was overexpressed in myocytes which attenutated the hypertrophy phenotype. Yeast two-hybrid experiments demonstrated an interaction of 16105 with hsp27 and/or troponin T.

[0098] The hsp27-16105 interaction predicts a role of 16105 in the regulation of actin polymerization which potentially leads to the hypertrophy of myocytes. The troponin T-16105 interaction suggests a role for 16105 in the regulation of the actomyosin ATPase resulting ultimately in a decrease in muscle contraction. Due to 16105 mRNA expression in the brain and heart and its upregulation in congestive heart failure tissue and hypertrophied myocytes, along with its functional role, modulators of 16105 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to congestive heart failure. 16105 polypeptides of the present invention are useful in screening for modulators of 16105 activity.

[0099] Gene ID 38650

[0100] The human 38650 sequence (SEQ ID NO:45), known also as an Adenosine Deaminase homolog, is approximately 1680 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 340 to 1407 of SEQ ID NO:45, encodes a 355 amino acid protein (SEQ ID NO:46).

[0101] As determined by TaqMan analysis, the highest expression of 38650 mRNA was found in heart and skeletal muscles. 38650 mRNA expression was also upregulated in human congestive heart failure (CHF) tissue.

[0102] 38650 is 22% identical to known Adenosine Deaminase (ADA). ADA catalyses the conversion of adenosine to inosine. Adenosine plasma levels are higher than normal in CHF patients. The elevation of adenosine is potentially cardioprotective and functions to reduce proinflammatory events. Inhibitors of 38650 would potentially function to increase adenosine levels and decrease TNF-alpha levels in the failing heart. In addition, increased adenosine levels in the blood due to the inhibition of 38650 would potentially stimulate other cardioprotective events such as: the inhibition of the growth of cardiac fibroblasts, vasodilation and reduction of inflammatory processes. Due to 38650 mRNA expression in the heart and skeletal muscles, along with its functional role, modulators of 38650 activity would be useful in treating disorders associated with cardiovascular disease. 38650 polypeptides of the present invention are useful in screening for modulators of 38650 activity.

[0103] Gene ID 14245

[0104] The human 14245 sequence (SEQ ID NO:47), known also as Muscle Specific Serine Kinase (MSSK1), is approximately 1835 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 25 to 1626 of SEQ ID NO:47, encodes a 533 amino acid protein (SEQ ID NO:48).

[0105] As determined by TaqMan analysis, 14245 mRNA expression was found to be upregulated in human heart and skeletal muscles. 14245 mRNA was also upregulated in human congestive heart failure tissues.

[0106] 14245 or MSSK1 is homologous to SRPK2 which is a protein kinase found to phosphorylate Ser/Arg rich splicing factors. The potential function of SRPK is in the regulation of pre-mRNA splicing. Several known genes are involved in splicing changes in heart failure tissue samples. These include, but are not limited to, L-type calcium channel alpha Ic, cardiac troponin T, Fas/Apol. Thus, 14245 or MSSK1 potentially plays a role in the splicing changes in genes contributing to congestive heart failure. Due to 14245 mRNA expression in the heart and skeletal muscles, along with its functional role, modulators of 14245 activity would be useful in treating disorders associated with cardiovascular disease. 14245 polypeptides of the present invention are useful in screening for modulators of 14245 activity.

[0107] Gene ID 58848

[0108] The human 58848 sequence (SEQ ID NO:49), known also as a novel kinase (putative serine/threonine), is approximately 1247 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 44 to 1090 of SEQ ID NO:49, encodes a 348 amino acid protein (SEQ ID NO:50).

[0109] As determined by TaqMan analysis, 58848 mRNA expression was upregulated in human heart tissue and to a lesser degree in skeletal muscle.

[0110] 58848 is a Ser/Thr kinase homologous to a zebrafish kinase and to a Ca/calmodulin dependent protein kinase. Due to 58848 mRNA expression in the heart and skeletal muscles, along with its functional role, modulators of 58848 activity would be useful in treating disorders associated with cardiovascular disease. 58848 polypeptides of the present invention are useful in screening for modulators of 58848 activity.

[0111] Gene ID 1870

[0112] The human 1870 sequence (SEQ ID NO:51), known also as GPR22, is approximately 1881 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 237 to 1538 of SEQ ID NO:51, encodes a 433 amino acid protein (SEQ ID NO:52).

[0113] As assessed by TaqMan analysis, 1870 mRNA expression was upregulated in human brain and congestive heart failure tissues. Due to 1870 mRNA expression in the brain and heart tissue, modulators of 1870 activity would be useful in treating disorders associated with cardiovascular disease. 1870 polypeptides of the present invention are useful in screening for modulators of 1870 activity.

[0114] Gene ID 25856

[0115] The human 25856 sequence (SEQ ID NO:53), known also as Pyroglutamyl Peptidase (pyrrolidone-carboxylate peptidase), is approximately 1626 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 218 to 808 of SEQ ID NO:53, encodes a 196 amino acid protein (SEQ ID NO:54).

[0116] As assessed by TaqMan analysis, 25856 mRNA was expressed in skeletal muscle and was regulated in human congestive heart failure tissue (CHF).

[0117] 25856 is a pyrrolidone-carboxylate pyroglutamyl peptidase (Pcp) type I. Type I pyroglutamyl peptidases are cytosolic proteins. They are involved in removing 5-oxoproline from various penultimate amino acid residues except L-Proline. Due to 25856 mRNA expression in the heart and skeletal muscles, along with its functional role, modulators of 25856 activity would be useful in treating disorders associated with cardiovascular disease. 25856 polypeptides of the present invention are useful in screening for modulators of 25856 activity.

[0118] Gene ID 32394

[0119] The human 32394 sequence (SEQ ID NO:55), known also as a voltage-gated potassium channel (KCNQ4), is approximately 2335 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 83 to 2170 of SEQ ID NO:55, encodes a 695 amino acid protein (SEQ ID NO:56).

[0120] As determined by TaqMan analysis, 32394 mRNA expression was upregulated in the fetal liver, megakaryocytes generated in vitro, the brain and in the heart. 32394 RNA was also expressed in the platelets from patients with coronary artery disease and in particular at higher levels in patients diagnosed with stable angina as compared with patients without coronary artery disease.

[0121] Although 32394 or KCNQ4 is found in sensory outer hair cells, and is mutated in dominant deafness [Cell 1999. 96(3):437-46], recent evidence indicates that at least three genes are mutated in deafness. Therefore, affecting the function of 32394 or KCNQ4 as an anti-thrombotic would not have an effect on hearing. The KCNQ4 channels are also implicated in regulating the activity of excitable cells [Am J Physiol Cell Physiol. 2001. 280(4):C859-66]. Since ion fluxes are important regulators of platelet reactivity, the restricted expression in megakaryocytes plus the elevated RNA levels of 32394 in the platelets of patients with stable angina suggests that 32394 plays an important role in the progression from stable to unstable acute vascular lesion. Due to 32394 mRNA expression in the brain, liver and heart, along with its functional role, modulators of 32394 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to thrombosis and atherosclerosis. 32394 polypeptides of the present invention are useful in screening for modulators of 32394 activity.

[0122] Gene ID 3484

[0123] The human 3484 sequence (SEQ ID NO:57), known also as a diacylglcerol kinase gamma (DGKγ), is approximately 3758 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 517 to 2892 of SEQ ID NO:57, encodes a 791 amino acid protein (SEQ ID NO:58).

[0124] As determined by TaqMan analysis, 3484 mRNA expression was upregulated in the brain, megakaryocytes generated in vitro and heart. 3484 mRNA was also expressed at relatively high levels in platelets from patients with and without coronary artery disease and from normal volunteers.

[0125] Platelet adhesion to collagen results in platelet activation. Phosphatidic acid levels increase upon platelet adhesion to collagen [Analytical Biochemistry. 1990. 187(1):173-178]. Phosphatidic acid also amplifies the thrombotic response by increasing platelet chemotaxis and aggregation [Platelets. 2001. 12(3):163-170]. 3484 or DGKγ potentially plays a critical role in platelet activation and aggregation following platelet adhesion to collagen via the platelet collagen receptor. Due to 3484 mRNA expression in the brain and heart, along with its functional role, modulators of 3484 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 3484 polypeptides of the present invention are useful in screening for modulators of 3484 activity.

[0126] Gene ID 345

[0127] The human 345 sequence (SEQ ID NO:59), known also as a melanocortin-1 receptor (MC1-R), a GPCR, is approximately 1270 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 169 to 1122 of SEQ ID NO:59, encodes a 317 amino acid protein (SEQ ID NO:60).

[0128] As determined by TaqMan analysis, 345 mRNA expression was upregulated the in heart, brain fetal liver, placenta, kidney, in umbilical cord blood, CD34+ cells and megakaryocytes generated in vitro. 345 RNA was also expressed in the platelets from patients with coronary artery disease and in normal volunteers.

[0129] The melanocortin-1 receptor or 345 is a Gs-linked receptor. Gs-linked receptors regulate adenyl cyclase, which is an important mediator of platelet activation. The presence of MCI-R in megakaryocytes and platelets indicates that regulating the activity of 345 potentially controls platelet activation and thrombosis. Due to 345 mRNA expression in the heart, brain fetal liver, placenta, kidney, in umbilical cord blood, CD34+ cells and megakaryocytes, along with its functional role, modulators of 345 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 345 polypeptides of the present invention are useful in screening for modulators of 345 activity.

[0130] Gene ID 9252

[0131] The human 9252 sequence (SEQ ID NO:61), known also as a hydroxymethyltransferase, is approximately 1599 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 13 to 1464 of SEQ ID NO:61, encodes a 483 amino acid protein (SEQ ID NO:62).

[0132] As determined by TaqMan analysis, 9252 mRNA was upregulated in the human liver when compared to normal liver tissues. Further analysis in a marmoset model showed 9252 regulation by cerivastatin in vivo.

[0133] Repression of 9252 reduces total cholesterol and triglycerides. 9252 gene expression regulates the hypolipidemic therapy cerivastatin. This regulation is identical to known genes involved in cholesterol biosynthesis (i.e. HMG CoA reductase). In addition, a known inhibitor of 9252 has lipid lowering effects in an in a rabbit vivo model. Due to 9252 mRNA expression in the liver, along with its functional role, modulators of 9252 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis. 9252 polypeptides of the present invention are useful in screening for modulators of 9252 activity.

[0134] Gene ID 9135

[0135] The human 9135 sequence (SEQ ID NO:63), known also as a fatty aldehyde dehydrogenase, is approximately 1791 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 164 to 1621 of SEQ ID NO:63, encodes a 485 amino acid protein (SEQ ID NO:64).

[0136] As determined by TaqMan analysis, 9135 mRNA was upregulated in the human liver when compared to normal liver tissues. Further analysis in a marmoset model showed 9135 regulation by cerivastatin in vivo.

[0137] Repression of fatty aldehyde dehydrogenase or 9135 potentially reduces total cholesterol and triglycerides. The fatty aldehyde dehydrogenase or 9135 gene is regulated by the hypolipidemic therapy cerivastatin. The regulation of 9135 is identical to known genes involved in cholesterol biosynthesis (i.e. HMG CoA reductase). In addition, fatty aldehyde dehydrogenase or 9135 is implicated in LTB4 degradation. LTB4 is a ligand for PPAR alpha. Inhibition of fatty aldehyde dehydrogenase or 9135 potentially results in increased levels of endogenous PPAR alpha ligand which is beneficial. Due to 9135 mRNA expression in the liver, along with its functional role, modulators of 9135 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis. 9135 polypeptides of the present invention are useful in screening for modulators of 9135 activity.

[0138] Gene ID 10532

[0139] The human 10532 sequence (SEQ ID NO:65), known also as a serine aminotransferase, is approximately 1487 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 22 to 1200 of SEQ ID NO:65, encodes a 392 amino acid protein (SEQ ID NO:66).

[0140] As determined by TaqMan analysis, 10532 mRNA was upregulated in the human liver when compared to normal liver tissues. Further analysis in a marmoset model showed 10532 regulation by cerivastatin/fenofibrate in vivo. In a human hepatocyte model, 10532 mRNA was also regulated by statin/PPAR alpha agonist in vitro. In addition, 10532 mRNA was also regulated by a high cholesterol diet in vivo.

[0141] Repression of serine aminotransferase or 10532 potentially reduces total cholesterol and triglycerides. 10532 gene expression is regulated by the hypolipidemic combination therapy cerivastatin/fenofibrate. 10532 is also regulated by high cholesterol diet. Regulation of 10532 is identical to known genes involved in cholesterol biosynthesis (i.e. HMG CoA reductase). Due to 10532 mRNA liver specific expression, along with its functional role, modulators of 10532 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis. 10532 polypeptides of the present invention are useful in screening for modulators of 10532 activity.

[0142] Gene ID 18610

[0143] The human 18610 sequence (SEQ ID NO:67), known also as melanoma alpha kinase, is approximately 7280 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 214 to 5871 of SEQ ID NO:67, encodes a 1885 amino acid protein (SEQ ID NO:68).

[0144] As determined by TaqMan analysis, 18610 mRNA was upregulated in heart tissue. 18610, an alpha kinase, functions in the action of calcium mediated cellular responses. The increase in calcium mediated signaling process in vasculature causes vasoconstriction. Therefore, the inhibition of alpha kinases or 18610 potentially results in lowering of calcium mediated signaling, thereby lowering blood pressure. Due to 18610 mRNA expression in the heart, along with its functional role, modulators of 18610 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis. 18610 polypeptides of the present invention are useful in screening for modulators of 18610 activity.

[0145] Gene ID 8165

[0146] The human 8165 sequence (SEQ ID NO:69), known also as an aspartyl aminopeptidase, is approximately 1696 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 152 to 1579 of SEQ ID NO:69, encodes a 475 amino acid protein (SEQ ID NO:70).

[0147] As determined by TaqMan analysis, the 8165 mRNA was upregulated in the human liver when compared to normal liver tissues. Further analysis in a marmoset model showed 8165 regulation by cerivastatin in vivo. In a human hepatocyte model, 8165 was also regulated by statin/PPAR alpha agonist in vitro.

[0148] Repression of aspartyl aminopeptidase potentially reduces total cholesterol and triglycerides. 8165 expression is regulated by the hypolipidemic therapy cerivastatin in vivo (marmosets) and in vitro (human hepatocytes). The regulation of 8165 is identical to known genes involved in cholesterol biosynthesis (i.e. HMG CoA reductase. Due to 8165 mRNA expression in the liver, along with its functional role, modulators of 8165 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis. 8165 polypeptides of the present invention are useful in screening for modulators of 8165 activity.

[0149] Gene ID 2448

[0150] The human 2448 sequence (SEQ ID NO:71), known also as a lysosphingolipid receptor (EDG3), is approximately 2327 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 1124 to 2260 of SEQ ID NO:71, encodes a 378 amino acid protein (SEQ ID NO:72).

[0151] As determined by TaqMan analysis, 2448 mRNA was highly expressed in human arteries, kidneys and cultured coronary smooth muscle cells. Further TaqMan analysis showed that 2448 mRNA was expressed in cultured human umbilical vein endothelial cells (HUVECs) and in heart tissue. In addition, rat models of vascular tone indicated that 2448 was upregulated in hypertensive rat aortas while downregulated in aortas of rats treated with antihypertensives.

[0152] 2448 or EDG3, is a lysosphingolipid receptor, with sphingosine 1-phosphate (SIP) as its ligand. SIP and 2448's involment in vascular tone and atherosclerosis is through the signaling cascades that the 2448 receptor triggers. 2448 is Gi, Gq and G12/13 coupled (Ann. Rev. Pharmacol. Toxicol., 2001, 41: 507-534) leading to the activation of Rho, Rac and MAPK signaling pathways while inhibiting the Adenylate cyclase pathway. The resulting intracellular Ca2+ mobilization (J Biochem, 2002, 362; 349-357) and kinase cascade activation plays a role in smooth muscle cell depolarization and the maintenance of vascular tone. Therefore, antagoning 2448 blocks the release of intracellular calcium and promotes hyperpolarization of the cell and vasorelaxation. Due to 2448 mRNA expression in the arteries, kidneys and cultured coronary smooth muscle cells brain, along with its functional role, modulators of 2448 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis and hypertension. 2448 polypeptides of the present invention are useful in screening for modulators of 2448 activity.

[0153] Gene ID 2445

[0154] The human 2445 sequence (SEQ ID NO:73), known also as a lysophosphatidic acid receptor (EDG2), is approximately 1576 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 27 to 1121 of SEQ ID NO:73, encodes a 364 amino acid protein (SEQ ID NO:74).

[0155] As determined by TaqMan analysis, 2445 mRNA was highly expressed in human arteries, cultured coronary smooth muscle cells and central nervous system (CNS) structures, such as spinal cord (SC), cortex, hypothalamus and dorsal root ganglion (DRG). Further TaqMan analysis indicated that 2445 mRNA was also present at lower levels in heart, kidney, skeletal muscle, adipose and various tissues of the immune system.

[0156] 2445 or EDG2, is a lysophosphatidic acid receptor, with LPA as its agonist. 2445 and its agonist, LPA, are involved in mutiple intracellular signaling cascades, including those involved in the maintenance of vascular tone and the development of atherosclerosis (Journal of Biological Chemistry, 2000, 2275: 27520-27530). The high expression of 2445 in peripheral blood vessels indicates a role for 2445 in vascular function. 2445 is Gi/o, Gq/11/14 and G12/13 coupled (Ann. Rev. Pharmacol. Toxicol., 2001, 41: 507-534). LPA stimulation leads to activation of the Ras-Raf-ERK pathway, adenylate cyclase inhibition, phospholipase D activation and Ca2+ mobilization. Stimulation of 2445 by LPA mobilizes intracellular Ca2+ via activation of phospholipase C (Molecular Pharmacology, 1998, 54: 881-888). Therefore, antagonizing 2445 blocks the release of intracellular calcium and activation of the ERK and Ras pathways and promotes hyperpolarization of the cell, leading to vasorelaxation. The receptor blockade also protects against smooth muscle cell proliferation which is prevalent in atherosclerosis. Due to 2445 mRNA expression in the arteries, cultured coronary smooth muscle cells, spinal cord, cortex, hypothalamus and dorsal root ganglion, along with its functional role, modulators of 2445 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to atherosclerosis and hypertension. 2445 polypeptides of the present invention are useful in screening for modulators of 2445 activity.

[0157] Gene ID 64624

[0158] The human 64624 sequence (SEQ ID NO:75), known also as a zinc tranporter (ZIP4), is approximately 2192 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 101 to 2044 of SEQ ID NO:75, encodes a 647 amino acid protein (SEQ ID NO:76).

[0159] As determined by TaqMan analysis, 64624 mRNA was expressed at the highest levels in kidney and brain. 64624 mRNA was also present at high levels in megakaryocytes generated in vitro. In addition, 64624 mRNA was present in the platelets of patients with coronary artery disease and from normal volunteers.

[0160] 64624 is a zinc transporter that has been implicated in dietary zinc uptake [AM J Hum Genet. 2002. 71(1):66-73]. Evidence suggests that zinc potentiates the aggregation response via the protein kinase C pathway [J Lab Clin Med. 1994. 123(1):102-109]. Zinc is also an important cofactor for the interaction of platelets with the coagulation mechanism. For example, zinc released from platelets acts as a cofactor for histidine-rich glycoprotein binding to heparin, preventing heparin from interacting with anti-thrombin III and thereby promoting fibrin formation [JBC 1997.272(21): 13541-47]. In addition, zinc is a cofactor of intrinsic coagulation activation. Therefore, regulation of the 64624 would provide a means to inhibit platelet-mediated thrombus formation. Due to 64624 mRNA expression in the kidney and brain, along with its functional role, modulators of 64624 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to thrombosis and atherosclerosis. 64624 polypeptides of the present invention are useful in screening for modulators of 64624 activity.

[0161] Gene ID 84237

[0162] The human 84237 sequence (SEQ ID NO:77), known also as a zinc tranporter (hzntl1), is approximately 2952 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 202 to 2499 of SEQ ID NO:77, encodes a 765 amino acid protein (SEQ ID NO:78).

[0163] As determined by TaqMan analysis, 84237 mRNA was expressed at highest levels in megakaryocytes generated in vitro, in fetal liver and brain. 84237 mRNA was also present at high levels in the platelets of patients with coronary artery disease and from normal volunteers.

[0164] 84237 or hzntl1 is the human ortholog to a murine zinc transporter, mzntl1. Zinc is an important cofactor for the interaction of platelets with the coagulation mechanism. For example, zinc released from platelets acts as a cofactor for histidine-rich glycoprotein binding to heparin, preventing heparin from interacting with anti-thrombin III and thereby promoting fibrin formation [JBC 1997.272(21):13541-47]. Zinc is also a cofactor of intrinsic coagulation activation. Evidence indicates that zinc potentiates the aggregation response via the protein kinase C pathway [J Lab Clin Med. 1994. 123(1): 102-109]. Therefore, regulation of the 84237, hzntl1, would provide a means to inhibit platelet-mediated thrombus formation. Due to 84237 mRNA expression in megakaryocytes generated in vitro and in fetal liver and brain, along with its functional role, modulators of 84237 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 84237 polypeptides of the present invention are useful in screening for modulators of 84237 activity.

[0165] Gene ID 8912

[0166] The human 8912 sequence (SEQ ID NO:79), known also as an alkyl-dihydroxyacetonephosphate synthase (alkyl-DHAP synthase), is approximately 2074 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 16 to 1992 of SEQ ID NO:79, encodes a 658 amino acid protein (SEQ ID NO:80).

[0167] As determined by TaqMan analysis, 8912 mRNA was expressed at the highest levels in brain, in fetal liver and in bone marrow progenitor cells expressing CD15. Further TaqMan experiments indicated that 8912 mRNA was present at high levels in megakaryocytes generated in vitro in kidney and in heart. 8912 mRNA was also present in the platelets from patients with and without coronary artery disease and from normal volunteers.

[0168] 8912 or alkyl-dihydroxyacetonephosphate synthase (alkyl-DHAP synthase) is a peroxisomal enzyme essential for the biosynthesis of ether phospholipids. Deficiencies in DHAP-synthase affects a specific phospholipid, plasmalogen, reducing its content in the plasma membrane of cells [J.B.C. 1998. 273(17):10296-10301; P.N.A.S. 1997. 94:4475-4480]. Lipid abnormalities exist in patients with diabetes. The platelets of diabetic patients are considered to be more reactive with regard to aggregation and thrombosis. Evidence exists demonstrating that in rodent models of diabetes, plasmalogen levels are altered [Int J. Biochem. 1994. 26(6):759-767]. Altered levels of alkyl-DHAP synthase found in the platelets of diabetic patients with coronary artery disease is found to contribute to the hyper-reactive phenotype associated with these diabetics' platelets. Due to 8912 mRNA expression in brain, in fetal liver and in bone marrow progenitor cells expressing CD15, along with its functional role, modulators of 8912 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 8912 polypeptides of the present invention are useful in screening for modulators of 8912 activity.

[0169] Gene ID 2868

[0170] The human 2868 sequence (SEQ ID NO:81), known also as a T-cell death associated gene (TDAG8), is approximately 1753 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 523 to 1536 of SEQ ID NO:81, encodes a 337 amino acid protein (SEQ ID NO:82).

[0171] As determined by TaqMan analysis, 2868 mRNA was predominantly expressed in lymphoid tissues, such as the spleen and tonsil. Further TaqMan experiments showed that 2868 mRNA was also expressed in human arteries and diseased aortas and some central nervous system structures, such as the spinal cord and hypothalamus. In pooled samples of diseased versus normal human arteries, there was a two-fold upregulation of 2868 mRNA in atherosclerotic vessels. In a rat model of hypertension, there was a downregulation of 2868 mRNA in the aortas of animals treated with anti-hypertensives, compared to their vehicle-treated controls.

[0172] Stimulation of 2868 results in increases in intracellular calcium and in inhibition of cAMP. Blockade of the 2868 receptor would result in a decreased immune response during the process of atherosclerotic lesion formation and would slow the progression of atherosclerosis. Due to 2868 mRNA expression in the spleen, tonsils, arteries, spinal cord and hypothalamus, along with its functional role, modulators of 2868 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis. 2868 polypeptides of the present invention are useful in screening for modulators of 2868 activity.

[0173] Gene ID 283

[0174] The human 283 sequence (SEQ ID NO:83), known also as a galanin receptor type 1 (Gal1-R), is approximately 1053 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 1 to 1050 of SEQ ID NO:83, encodes a 349 amino acid protein (SEQ ID NO:84).

[0175] As determined by TaqMan analysis, 283 mRNA was highly expressed in the central nervous system (CNS), particularly the brain and spinal cord. Further Taqman analysis indicated that 283 mRNA was expressed in the human kidneys, arteries and veins. The 283 gene product was also detected in rat tissues and was down-regulated in kidneys of rats which were sensitive to salt-induced hypertension. Our data showed an enrichment of 283 over the other galanin receptors in the kidney.

[0176] Galanin stimulation of 283 or Gal 1-R causes a decrease in cAMP in the cell and the opening of inwardly rectifying K+ channels (TiPS, March 2000, 21: 109-117). The high expression of the 283 receptor in CNS structures suggests a central functional role. Our data, describing good expression in peripheral tissues, particularly the kidney and vessels, suggest a novel role for this receptor in cardiovascular function. Therefore, antagonising the 283 receptor would prevent the influx of K+ and increase the intracellular levels in cAMP, promoting hyperpolarization of the cell and vasorelaxation. Due to 283 mRNA expression in the brain, spinal cord, kidney, arteries and veins, along with its functional role, modulators of 283 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to atherosclerosis. 283 polypeptides of the present invention are useful in screening for modulators of 283 activity.

[0177] Gene ID 2554

[0178] The human 2554 sequence (SEQ ID NO:85), known also as mGlut8 receptor, is approximately 3321 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 58 to 2784 of SEQ ID NO:85, encodes a 908 amino acid protein (SEQ ID NO:86).

[0179] As determined by TaqMan analysis, 2554 mRNA was expressed in the liver. Further Taqman analysis on specific rodent models of cardiovascular disease indicated that 2554 mRNA was upregulated in vitro in statin/PPAR (peroxisomal proliferators activated receptor) models. 2554 mRNA was also repressed by cholesterol in apolipop protein (apo E) cholesterol models, but upregulated in choletryramine models. 2554 plays a potential role in mediating the effects on hepatic TG. Therefore, inhibiting 2554 potentially has beneficial effects on lipid profiles.

[0180] As determined by TaqMan analysis, 2554 mRNA expression was upregulated in 5-fold in failing vs. normal human hearts. The human metabotropic Glutamate receptor type 8 (mGlu8) belongs to the superfamily of G-protein-coupled receptors (GPCRs). This receptor is a member of the group III metabotropic glutamate receptors, which also includes mGlu4, mGlu6 and mGlu7. Glutamate is a neurotransmitter commonly known to produce excitatory effects in the mammalian central nervous system. Scientific literature has also demonstrated that glutamate levels decrease in ischemic hearts. Since mGlu8 can affect intracellular levels of cAMP due to its coupling via Gi, upregulation of the expression of mGlu8 has direct effects on contractility of the heart. Thus, mGlu8 may potentially be implicated in cardiovascular diseases, such as ischemia and heart failure.

[0181] Due to 2554 mRNA expression in the liver and in failing human heart, along with its functional role, modulators of 2554 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis, dyslipidemia, ischemia and heart failure. 2554 polypeptides of the present invention are useful in screening for modulators of 2554 activity.

[0182] Gene ID 9464

[0183] The human 9464 sequence (SEQ ID NO:87), known also as an ATP dependent inward rectifying K channel, is approximately 2896 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 439 to 1578 of SEQ ID NO:87, encodes a 379 amino acid protein (SEQ ID NO:88).

[0184] As determined by TaqMan analysis, 9464 mRNA was expressed in the liver. Further Taqman analysis on specific rodent models of cardiovascular disease indicated that 9464 mRNA was repressed in apolipop protein (apo E) cholesterol models. Published literature indicates that ligands for the 9464 receptor have beneficial lipid lowering effects in pre-clinical models. Therefore, anatagonists and agonists of 9464 potentially have beneficial effects on lipid profiles. Due to 9464 mRNA expression in the liver, along with its functional role, modulators of 9464 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to atherosclerosis and dyslipidemia. 9464 polypeptides of the present invention are useful in screening for modulators of 9464 activity.

[0185] Gene ID 17799

[0186] The human 17799 sequence (SEQ ID NO:89), known also as a cytidyl transferase, is approximately 1856 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 67 to 1236 of SEQ ID NO:89, encodes a 389 amino acid protein (SEQ ID NO:90).

[0187] As determined by TaqMan analysis, indicated that 17799 mRNA was expressed in the human liver. Further TaqMan analysis on specific models of cardiovascular disease indicated that 17799 mRNA was repressed in apolipop protein (apo E) cholesterol models and niacin marmoset models. Published literature indicates that the 17799 enzyme is linked to Phosphoethanolamine (PE) biosynthesis and increased PE biosynthesis is associated with increased levels of TG transport from hepatocytes. PE is also pro-thrombotic and PE is a target for glycation, enhancing the atherosclerotic potential of LDL. Inhibition of 17799 potentially has beneficial effects on lipid profiles. Due to 17799 mRNA expression in the human liver, along with its functional role, modulators of 17799 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to atherosclerosis and dyslipidemia. 17799 polypeptides of the present invention are useful in screening for modulators of 17799 activity.

[0188] Gene ID 26686

[0189] The human 26686 sequence (SEQ ID NO:91), known also as acyl co A synthase, is approximately 3165 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 420 to 2582 of SEQ ID NO:91, encodes a 720 amino acid protein (SEQ ID NO:92).

[0190] As determined by TaqMan analysis, 26686 mRNA was expressed in the liver. Further Taqman analysis on specific models of cardiovascular disease indicated that 26686 mRNA was upregulated in feno/ceriva marmoset and statin/PPAR (peroxisomal proliferators activated receptor) in vitro hep models, but 26686 mRNA showed a decreased expression leves in monkey cholesterol and apolipop protein (apo E) cholesterol models. Published literature indicates that 26686 plays a role of in lipid metabolism. Therefore, inhibiting 26686 potentially leads to lower lipid levels. Due to 26686 mRNA expression in the liver, along with its functional role, modulators of 26686 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis and dyslipidemia. 26686 polypeptides of the present invention are useful in screening for modulators of 26686 activity.

[0191] Gene ID 43848

[0192] The human 43848 sequence (SEQ ID NO:93), known also as N-acyltransferase, is approximately 1124 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 135 to 1025 of SEQ ID NO:93, encodes a 296 amino acid protein (SEQ ID NO:94).

[0193] As determined by TaqMan analysis, 43848 mRNA was increased in cholestyramine and fenofibrate/cerivastatin marmoset models, but 43848 expression levels were decreased in apolipop protein (apo E) cholesterol model. Published literature indicates that 43848 is part of the FXR nuclear receptor negative feedback loop for bile acid synthesis. Antagonist for FXR results in cholesterol reduction. Therefore, inhibiting 43848 has beneficial effects on lipid profiles. Due to 43848 mRNA expression in cholestyramine and fenofibrate/cerivastatin marmoset models, along with its functional role, modulators of 43848 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis and dyslipidemia. 43848 polypeptides of the present invention are useful in screening for modulators of 43848 activity.

[0194] Gene ID 32135

[0195] The human 32135 sequence (SEQ ID NO:95), known also as tetrahydrofolate dehydrogenase, is approximately 3040 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 111 to 2819 of SEQ ID NO:95, encodes a 902 amino acid protein (SEQ ID NO:96).

[0196] As determined by TaqMan analysis, 32135 mRNA was expressed in the human liver. Taqman analysis on specific models of cardiovascular disease indicated that 32135 mRNA was repressed in apolipop protein (apo E) cholesterol, monkey cholesterol and niacin models. Published literature indicates that mutations in methylene tetrahydrofolate reductase associated with elevated homocysteine levels. 32135 plays a potential role in homocysteine biosynthesis. Therefore, inhibiting 32135 has beneficial effects on lipid profiles. Due to 32135 mRNA expression in the liver, along with its functional role, modulators of 32135 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis and dyslipidemia. 32135 polypeptides of the present invention are useful in screening for modulators of 32135 activity.

[0197] Gene ID 12208

[0198] The human 12208 sequence (SEQ ID NO:97), known also as a human small conductance calcium-activated potassium channel protein 3 (KCNN3), is approximately 3095 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 334 to 2544 of SEQ ID NO:97, encodes a 736 amino acid protein (SEQ ID NO:98).

[0199] As determined by TaqMan analysis, 12208 mRNA was expressed in the spleen, kidney, heart and brain. Further TaqMan analysis indicated that 12208 was expressed at high levels in megakaryocytes generated in vitro. In addition, 12208 RNA is detected at high levels in the platelets of patients with coronary artery disease and in platelets from normal volunteers.

[0200] The calcium-activated potassium channel, KCNN3 or 12208 is activated by intracellular calcium. Calcium spikes are an essential component of platelet activation. Increased levels of KCNN3 or 12208 in the platelets of patients with stable angina, indicates an increased platelet reactivity in these patients. Therefore, inhibition of KCNN3 or 12208, provides a means to inhibit platelet aggregation and thrombus formation. Due to 12208 mRNA expression in the spleen, kidney, heart and brain, along with its functional role, modulators of 12208 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to thrombosis and atherosclerosis. 12208 polypeptides of the present invention are useful in screening for modulators of 12208 activity.

[0201] Gene ID 2914

[0202] The human 2914 sequence (SEQ ID NO:99), known also as a mosaic serine protease, is approximately 2393 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 88 to 1833 of SEQ ID NO:99, encodes a 581 amino acid protein (SEQ ID NO:100).

[0203] As determined by TaqMan analysis, 2914 mRNA was expressed at the highest levels in megakaryocytes generated in vitro and in placenta. Further Taqman analysis indicated that 2914 RNA is detected in the platelets of patients with coronary artery disease

[0204] The mosaic serine protease or 2914 is spliced with and without a transmembrane domain [BBA 2001. 19;1518(1-2):204-409]. Serine proteases play an essential role in maintaining hemostasis and in promoting thrombogenesis. Therefore, inhibition of the mosaic serine protease, 2914, would provide a means to inhibit thrombus formation. Due to 2914 mRNA expression in megakaryocytes generated in vitro and in the placenta, along with its functional role, modulators of 2914 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 2914 polypeptides of the present invention are useful in screening for modulators of 2914 activity.

[0205] Gene ID 51130

[0206] The human 51130 sequence (SEQ ID NO:101), known also as an peptidylarginine deiminase (PAD), is approximately 2263 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 27 to 2018 of SEQ ID NO: 101, encodes a 663 amino acid protein (SEQ ID NO: 102).

[0207] As determined by TaqMan analysis, 51130 mRNA was expressed in hematopoietic cells and mononuclear cells and CD14 positive cells (monocytes). Further TaqMan analysis indicated that 51130 mRNA was present at high levels in megakaryocytes generated in vitro and in the platelets of patients with coronary artery disease and from normal volunteers.

[0208] PAD (51130) is a peptidylarginine deiminase that is implicated in myeloid differentiation [JBC. 1999. 274(39):27786-27792]. Recent results indicate that PAD converts an essential arginine residue on antithrombin III (ATIII) to citrulline, thereby negatively affecting the function of this important anticoagulant. Deimination of antithrombin III results in an increased affinity of ATIII for heparin thus inactivating the thrombin-neutralizing function of ATIII [JBC 1997. 272(32): 19652-19655]. The inactivation of ATIII by platelet released PAD or 51130 would create an imbalance in hemostasis by accelerating thrombin activation of platelets and fibrin formation. Therefore, inhibition of the platelet peptidylarginine deiminase provides a means to inhibit platelet-mediated thrombus formation. Due to 51130 mRNA expression in hematopoietic cells and mononuclear cells, along with its functional role, modulators of 51130 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 51130 polypeptides of the present invention are useful in screening for modulators of 51130 activity.

[0209] Gene ID 19489

[0210] The human 19489 sequence (SEQ ID NO: 103), known also as a novel secreted phospholipase A2 (sPLA2), is approximately 1204 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 143 to 712 of SEQ ID NO: 103, encodes a 189 amino acid protein (SEQ ID NO:104).

[0211] As determined by TaqMan analysis, 19489 mRNA was expressed in megakaryocytes generated in vitro, in erythroid cells and in heart. In addition, 19489 RNA was present at very high levels in the platelets of patients with coronary artery disease and from normal volunteers

[0212] sPLA2 or 19489 is a novel secreted phospholipase A2 with as of yet an undefined function [JBC. 2000. 275(51):39823-39826]. Lysophosphatidic acid is a lipid mediator and platelet agonist. Lysophosphatidic acid also binds and activates endothelial cells. Lysophosphatidic acid is generated by the enzymatic activity of phospholipases. The high levels of sPLA2 or 19489 in platelets and its restricted expression indicate that sPLA2 or 19489 is an important enzyme during acute coronary syndrome. SPLA2 or 19489 is potentially responsible for the generation of lysophosphatidic acid and its increased plasma levels following acute coronary events. Therefore, inhibition of the platelet sPLA2 or 19489, would inhibit platelet-endothelial cell interactions and thrombus formation. Due to 19489 mRNA expression in megakaryocytes generated in vitro, in erythroid cells and in heart, along with its functional role, modulators of 19489 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 19489 polypeptides of the present invention are useful in screening for modulators of 19489 activity.

[0213] Gene ID 21833

[0214] The human 21833 sequence (SEQ ID NO: 105), known also as the enzyme kynureninase, is approximately 1637 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 107 to 1504 of SEQ ID NO:105, encodes a 465 amino acid protein (SEQ ID NO:106).

[0215] As determined by TaqMan analysis, 21833 mRNA was expressed at highest levels in the human liver, in macrophages and tonsil. Further TaqMan analysis indicated that 21833 mRNA was upregulated in diseased human arteries when compared to normal vessels. In cultured human monocytes and macrophages, 21833 was upregulated after interferon gamma and CD40-ligand stimulation. By laser capture microdissection and TM analysis, 21833 was enriched in the macrophage and monocyte-rich lesion area of atherosclerotic arteries.

[0216] 21833 or kynureninase is a downstream enzyme involved in tryptophan metabolism (Saito et al., AJP-Renal Physiology, 279: 3, F565-F572, 2000). Kynureninase converts kynurenine to anthranilic acid and 3-hydroxykynurenine to 3-hydroxyanthranilic acid. The downstream product of 3-hydroxyanthranilic acid metabolism is quinolinic acid formation. Quinolinic acid is an agonist of the NMDA-receptor and is excitotoxic to neural cells; it has been found in macrophages stimulated by interferon gamma and TNFalpha (Chiarugi, A et al., Journal of Neuroimmunology, 120: 1-2, 190-198.) Therefore, inhibiting 21833 or kynureninase leads to the reduction of the toxin, quinolinic acid, which can reduce atherosclerotic injury in vessels. Due to 21833 mRNA expression in the human liver, in macrophages and tonsil, along with its functional role, modulators of 21833 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to thrombosis and atherosclerosis. 21833 polypeptides of the present invention are useful in screening for modulators of 21833 activity.

[0217] Gene ID 2917

[0218] The human 2917 sequence (SEQ ID NO:107), known also as serine protease 23, is approximately 1647 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 105 to 1256 of SEQ ID NO: 107, encodes a 383 amino acid protein (SEQ ID NO:108).

[0219] As determined by TaqMan analysis, 2917 mRNA was expressed at highest levels in human arteries, veins, HUVECs, smooth muscle cells and vascular rich organs. By transcriptional profiling, there was upregulation of 2917 mRNA in response to anti-hypertensive therapy in normotensive rat aortas. By angiotensinl receptor blockade, L-type calcium channel blockade and by ATP-dependent potassium channel opening indicated that 2917 mRNA was upregulated.

[0220] Serine protease 23 or 2917 is a novel serine protease cloned from human umbilical vein endothelial cells. Its abundance in vascularized tissues such as the aorta, vein, heart and kidney; its presence in endothelial cells and smooth muscle cells; and its regulation in a rat model of vascular tone gene discovery, implicate 2917 in the maintenance of systemic blood pressure. Therefore, antagonists of 2917 would function in the reduction of peripheral vascular resistance and decrease blood pressure. Due to 2917 mRNA expression in the arteries, veins, HUVECs, smooth muscle cells and vascular rich organs, along with its functional role, modulators of 2917 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to thrombosis and atherosclerosis. 2917 polypeptides of the present invention are useful in screening for modulators of 2917 activity.

[0221] Gene ID 59590

[0222] The human 59590 sequence (SEQ ID NO: 109), known also as heart alpha-kinase (HAK), is approximately 5375 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 199 to 4794 of SEQ ID NO: 109, encodes a 1531 amino acid protein (SEQ ID NO:110).

[0223] As determined by TaqMan analysis, 59590 mRNA was upregulated in the experiments comparing human heart left ventricle samples of 12 congestive heart failure patients (CHF) with 7 non-failing patients (NF, control). 59590 mRNA expression was restricted to heart and skeletal muscle and was expressed to a lesser degree in kidney, osteoblasts and smooth muscle cells.

[0224] Heart alpha-kinase (HAK) or 59590 belongs to a new family of kinases (alpha-kinases) that is unlike the conventional serine/threonine/tyrosine kinases. Family members include eukaryotic elongation factor-2 kinase (eEF-2K) and Dictyostelium's myosin heavy chain kinase A, B and C (MHCK A, B and C). HAK or 59590 is highly expressed in heart and skeletal muscle and is regulated in heart failure. Because HAK or 59590 belongs to the same class as Dictyostelium's MHCK A, HAK or 59590 potentially plays a role in sarcomere assembly and in contraction efficiency which is known to be impaired in heart failure patients. Muscle contracts when cytosolic calcium is increased (released from sarcoplasmic reticulum at every cycle) through actomyosin interactions that forms part of the sarcomere. During the progression of heart failure, the myocytes try to compensate for an increase workload by increasing in size (hypertrophy). At the late stage of heart failure, there is loss of contractile elements, marked disruption of Z bands and a severe disruption of the normal parallel arrangement of sarcomere resulting in impaired contraction. The upregulation of HAK or 59590 in heart failure potentially causes the impaired contraction. Therefore inhibitors to HAK or 59590 are beneficial in the treatment of heart failure and other cardiovascular disorders. Due to 59590 mRNA expression in the heart and skeletal muscle, along with its functional role, modulators of 59590 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to ischemia and heart failure. 59590 polypeptides of the present invention are useful in screening for modulators of 59590 activity.

[0225] Gene ID 15992

[0226] The human 15992 sequence (SEQ ID NO: 111), known also as cardiolipin synthase, is approximately 1241 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 94 to 999 of SEQ ID NO:111, encodes a 301 amino acid protein (SEQ ID NO:112).

[0227] As determined by TaqMan analysis, 15992 mRNA showed a 5 fold upregulation in ischemic versus normal heart samples in ischemic heart samples. Further Taqman analysis indicated that 15992 mRNA expresssion was restricted with the highest level in CHF heart followed by lower levels of expression in colon tumor, prostate tumor and normal adrenal gland.

[0228] Cardiolipin synthase is a member of this family of transferases and cardiolipin, associated primarily with the inner mitochondrial membrane of mammalian cells, comprises approximately 15% of the entire cardiac glycerolphospholipid mass. Cardiolipin is required for a number of mitochondrial enzymes involved in energy metabolism; content of cardiolipin is important for activation of these enzymes. Ischemic events will decrease the cardiolipin content as well as the level of phosphorylation through cytochrome oxidase. Cardiolipin is enriched in oxidatively sensitive acyl residues, addition of cardiolipin but not peroxidized cardiolipin will almost completely restore activity of cytochrome oxidase. Therefore, the upregulation of 15992 potentially results in either synthesis of an alternate phospholipid that replaces cardiolipin in the mitochondrial membrane or alters its molecular composition resulting in a decrease in cytochrome oxidase activity. Due to 15992 mRNA expression in the brain and heart, along with its functional role, modulators of 15992 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to ischemia and heart failure. 15992 polypeptides of the present invention are useful in screening for modulators of 15992 activity.

[0229] Gene ID 2094

[0230] The human 2094 sequence (SEQ ID NO: 113), known also as human germinal center kinase (GCK), which is approximately 2906 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 40 to 2499 of SEQ ID NO: 113, encodes a 765 amino acid protein (SEQ ID NO: 114).

[0231] As determined by TaqMan analysis, 2094 mRNA was expressed at highest levels in brain and in megakaryocytes generated in vitro. 2094 mRNA was also present in the placenta. Further TaqMan analysis indicated that 2094 mRNA was detected in the platelets of apheresed normal donors and in the platelets of patients with coronary artery disease and in platelets from normal volunteers. 2094 mRNA was also present at statistically significant elevated levels in the platelets of patients with angina as compared with patients with no coronary artery disease or normal volunteers.

[0232] The germinal center kinase, GCK or 2094, activates at least two MAP kinases, MEKK1 and MLK3 [MCB. 2002. 22(3):737-749]. MLK3 activates MKK4 through a phosphorylation event, and MKK4 activates JNK kinase also by phosphorylation [JBC.2000. 275(36);27893-27900]. JNK activation is required for platelet aggregation. GCK or 2094 also activates MEKK1 inducing autophosphorylation of MEKK1 however, evidence exists indicating that MEKK1 is not a mediator of platelet aggregation [JBC. Sep. 2, 2002 3 9epub ahead of print]. The high levels of 2094 mRNA found in platelets and the elevated levels found in the platelets of patients with angina indicates that 2094 regulates JNK-mediated platelet aggregation. Therefore, inhibiting 2094 provides a means to inhibit platelet-rich thrombus formation. Due to 2094 mRNA expression in the brain and in megakaryocytes, along with its functional role, modulators of activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to thrombosis and atherosclerosis. 2094 polypeptides of the present invention are useful in screening for modulators of 2094 activity.

[0233] Gene ID 2252

[0234] The human 2252 sequence (SEQ ID NO: 115), known also as a human germinal center kinase III (MASK), is approximately 3335 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 221 to 1471 of SEQ ID NO: 115, encodes a 416 amino acid protein (SEQ ID NO: 116).

[0235] As determined by TaqMan analysis, 2252 mRNA was expressed in placenta and peripheral blood mononuclear cells. 2252 mRNA was expressed at high levels in megakaryocytes generated in vitro. In addition, 2252 mRNA is detected in the platelets of apheresed normal donors and at high levels in the platelets of patients with coronary artery disease and in platelets from normal volunteers.

[0236] 2252 is also known as germinal center kinase III subfamily member known as MASK. MASK or 2252 activity has been implicated in apoptosis [JBC. 2002. 277(8):5929-5939]. Recent reports compare the mechanisms driving platelet activation and degranulation to the apoptotic pathway [Blood.1999. 93(12):4222-4231]. Based on the literature and expression data, 2252 or MASK is a required signaling component regulating platelet activation and degranulation. Therefore, inhibition of 2252 or MASK, would inhibit platelet aggregation and thrombus formation. Due to 2252 mRNA expression in placenta, peripheral blood mononuclear cells and megakaryocytes generated in vitro, along with its functional role, modulators of 2252 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 2252 polypeptides of the present invention are useful in screening for modulators of 2252 activity.

[0237] Gene ID 3474

[0238] The human 3474 sequence (SEQ ID NO: 117), known also as vesicular neurotransmitter transporter (VMAT2), is approximately 1800 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 114 to 1658 of SEQ ID NO: 117, encodes a 514 amino acid protein (SEQ ID NO: 118).

[0239] As determined by TaqMan analysis, 3474 mRNA was predominantly expressed in megakaryocytes, CD34+ progenitor cells and platelets. Further Taqman analysis also detected 3474 mRNA in normal human ovary.

[0240] The vesicular neurotransmitter transporter, VMAT2 or 3474, is known to sequester monoamines within synaptic vesicles. VMAT2 or 3474's expression in platelets indicate a similar function of sequestering monoamines within platelet granules. Platelet granule content is released upon platelet aggregation and is essential to the development of a thrombus. Our data indicates that this function is regulated in the platelets of patients with acute coronary syndromes, myocardial infarction and unstable angina as compared with patients with stable angina. Therefore, regulating 3474 or VMAT2 protects against the development of acute coronary syndromes. Due to 3474 mRNA expression in megakaryocytes, CD34+ progenitor cells and platelets, along with its functional role, modulators of 3474 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 3474 polypeptides of the present invention are useful in screening for modulators of 3474 activity.

[0241] Gene ID 9792

[0242] The human 9792 sequence (SEQ ID NO: 119), known also as human high-affinity cationic amino acid transporter-1 (CAT-1), is approximately 2157 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 148 to 2037 of SEQ ID NO: 119, encodes a 629 amino acid protein (SEQ ID NO: 120).

[0243] As determined by TaqMan analysis, 9792 mRNA was expressed at highest levels in red blood cells and in megakaryocytes generated in vitro. Further TaqMan analysis indicated that 9792 mRNA was present in placenta and brain. In addition, 9792 mRNA was present in the platelets of patients with angina and in platelets from normal volunteers.

[0244] 9792 or CAT-1 is a cationic amino acid transporter involved in the transport of arginine, a precursor to the vasoamine, nitric oxide. Ischemia-reperfusion injury is a serious complication resulting from current treatments for clot resolution in the acute coronary syndromes. While endogenous production of nitric oxide is important for vascular tone, recent evidence suggests controlling the concentration of nitric oxide is essential to preventing vascular injury and arryhthmias [J AM Coll Crdiol. 2001.38(2):546-554]. Regulation of CAT-1 on platelets provides a means to control nitric oxide production and the associated free radical injury following ischemia-reperfusion that occurs during thrombus formation and resolution. Therefore, inhibition of CAT-1 or 9792 protects against secondary coronary events. Due to 9792 mRNA expression in red blood cells and megakaryocytes generated in vitro, along with its functional role, modulators of 9792 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 9792 polypeptides of the present invention are useful in screening for modulators of 9792 activity.

[0245] Gene ID 15400

[0246] The human 15400 sequence (SEQ ID NO:121), known also as a human germinal center kinase called Traf2 and NCK interacting kinase (TNIK), is approximately 3807 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 1 to 3807 of SEQ ID NO: 121, encodes a 1268 amino acid protein (SEQ ID NO: 122).

[0247] As determined by TaqMan analysis, 15400 mRNA was expressed in brain and megakaryocytes generated in vitro. 15400 mRNA was detected in the platelets of apheresed normal donors and at high levels in the platelets of patients with coronary artery disease and in platelets from normal volunteers.

[0248] The germinal center kinase, 15400 or TNIK, activates the JNK signaling pathway [JBC. 1999. 273(43):30729-30737]. In vitro derived evidence suggests that exposure of platelets to VWF or thrombin activates JNK [Br J Haematol. 2000.109(4):851-856]. 15400 or TNIK is also implicated in actin based cytoskeletal reorganization. 15400 or TNIK phosphorylates gelsolin, the F-actin severing protein, in TNIK transfected cells [JBC. 1999. 273(43):30729-30737]. Shape change is an early step in platelet activation and requires gelsolin activity for actin reorganization [J Cell Biol. 1996.134(2):389-399]. Based on the literature and expression data, 15400 or TNIK plays an early step in platelet activation. Therefore, inhibition of TNIK, 15400, provides a means to inhibit platelet activation and thrombus formation. Due to 15400 mRNA expression in brain and megakaryocytes generated in vitro, along with its functional role, modulators of 15400 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to thrombosis and atherosclerosis. 15400 polypeptides of the present invention are useful in screening for modulators of 15400 activity.

[0249] Gene ID 1452

[0250] The human 1452 sequence (SEQ ID NO:123), known also as fgr kinase, is approximately 2354 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 20 to 2218 of SEQ ID NO: 123, encodes a 529 amino acid protein (SEQ ID NO: 124).

[0251] As determined by TaqMan analysis, 1452 mRNA was expressed in a variety of human tissues, including heart, spleen, pancreas, lung and tonsil. Further TaqMan analysis indicated that 1452 mRNA was expressed in macrophages, neutrophils, and erythroid progenitor cells. 1452 mRNA was also expressed in normal and atherosclerotic human arteries. In ApoE knockout mouse aortas, there was a substantial increase in expression of 1452 mRNA expression in the aortic arches compared to abdominal aortas; this expression was highly correlated with CD68 levels, indicating that 1452 mRNA was enriched in the macrophage rich lesion compartment of the vessel. In addition, 1452 mRNA was robustly expressed in cultured human monocytes and macrophages.

[0252] 1452 is a member of the src family of tyrosine kinases and is also called fgr kinase (Notario et al., J Cell Biol, 1989, 109: 3129-3136). It is thought that 1452 activity is partly responsible for macrophage migration and spreading. Given that macrophage recruitment and infiltration are a major aspect of the disease process in vessel wall atherosclerosis, inhibiting 1452 would result in a reduction of macrophage and eventually foam cell content in an atherosclerotic plaque and a diminished lesion size. Due to 1452 mRNA expression in the heart, spleen, pancreas, lung, tonsil, macrophages, neutrophils, and erythroid progenitor cells, along with its functional role, modulators of 1452 activity would be useful in treating disorders associated with cardiovascular disease, including but not limited to atherosclerosis. 1452 polypeptides of the present invention are useful in screening for modulators of 1452 activity.

[0253] Gene ID 6585

[0254] The human 6585 sequence (SEQ ID NO:125), known also as acyl peptide hydrolase, is approximately 2374 nucleotides long including untranslated regions. The coding sequence, located at about nucleic acid 20 to 2218 of SEQ ID NO:125 encodes a 732 amino acid protein (SEQ ID NO:126).

[0255] As determined by TaqMan analysis, 6585 mRNA was highly expressed in human arteries, umbilical vein endothelial cells, coronary smooth muscle cells, congestive heart failure samples, kidneys, skeletal muscle and brain cortex. There was significant (t-test, p=0.01) upregulation demonstrated across human heart failure samples compared to non-failing ventricles. In rats, 6585 mRNA was moderately expressed in aortas. In 15 week old spontaneously hypertensive-stroke prone rats, there was trend toward upregulation of 6585 mRNA compared to Wistar Kyoto normotensive controls (not significant, p=0.0527).

[0256] 6585 is known as acyl peptide hydrolase, a member of a group of serine peptidases from the prolyl oligopeptidase family. Prolyl oligopeptidase is involved in blood pressure control and amnesia (Polgar L., The prolyl oligopeptidase family. Cell Mol Life Sci February 2002;59(2):349-62). The enriched expression of the 6585 gene product in human vessels and the upregulation of 6585 in human failing myocardium as well as hypertensive rat aortas, indicates that 6585 plays multiple roles in the cardiovascular system. Specifically, antagonism of 6585 should reduce vascular tone and potentially reduce the progression of damage in congestive heart failure. Due to 6585 mRNA expression in human arteries, umbilical vein endothelial cells, coronary smooth muscle cells, hearts in congestive heart failure, kidneys, skeletal muscle and brain cortex, along with its functional role, modulators of 6585 activity would be useful in treating disorders associated with cardiovascular disease including but not limited to ischemia and heart failure. 6585 polypeptides of the present invention are useful in screening for modulators of 6585 activity.

[0257] Various aspects of the invention are described in further detail in the following subsections:

[0258] Screening Assays:

[0259] The invention provides a method (also referred to herein as a “screening assay”) for identifying modulators, i.e., candidate or test compounds or agents (e.g., peptides, peptidomimetics, small molecules (organic or inorganic) or other drugs) which bind to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins, have a stimulatory or inhibitory effect on, for example, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity, or have a stimulatory or inhibitory effect on, for example, the expression or activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate. Compounds identified using the assays described herein may be useful for treating cardiovascular diseases, e.g., atherosclerosis and/or thrombosis.

[0260] These assays are designed to identify compounds that bind to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, bind to other intracellular or extracellular proteins that interact with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, and interfere with the interaction of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein with other intercellular or extracellular proteins. For example, in the case of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, which is a transmembrane receptor-type protein, such techniques can identify ligands for such a receptor. A 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein ligand or substrate can, for example, be used to ameliorate cardiovascular diseases, e.g., atherosclerosis, ischemia/reperfusion, hypertension, restenosis, arterial inflammation, thrombosis and endothelial cell disorders. Such compounds may include, but are not limited to peptides, antibodies, or small organic or inorganic compounds. Such compounds may also include other cellular proteins.

[0261] Compounds identified via assays such as those described herein may be useful, for example, for ameliorating cardiovascular disease, e.g., athersclerosis and/or thrombosis. In instances whereby a cardiovascular disease condition results from an overall lower level of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression and/or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein in a cell or tissue, compounds that interact with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein may include compounds which accentuate or amplify the activity of the bound 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Such compounds would bring about an effective increase in the level of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein activity, thus ameliorating symptoms.

[0262] In other instances, mutations within the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene may cause aberrant types or excessive amounts of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins to be made which have a deleterious effect that leads to a cardiovascular disease. Similarly, physiological conditions may cause an excessive increase in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression leading to a cardiovascular disease. In such cases, compounds that bind to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein may be identified that inhibit the activity of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Assays for testing the effectiveness of compounds identified by techniques such as those described in this section are discussed herein.

[0263] In one embodiment, the invention provides assays for screening candidate or test compounds which are substrates of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or polypeptide or biologically active portion thereof. In another embodiment, the invention provides assays for screening candidate or test compounds which bind to or modulate the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or polypeptide or biologically active portion thereof. The test compounds of the present invention can be obtained using any of the numerous approaches in combinatorial library methods known in the art, including: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the ‘one-bead one-compound’ library method; and synthetic library methods using affinity chromatography selection. The biological library approach is limited to peptide libraries, while the other four approaches are applicable to peptide, non-peptide oligomer or small molecule libraries of compounds (Lam, K. S. (1997) Anticancer Drug Des. 12:145).

[0264] Examples of methods for the synthesis of molecular libraries can be found in the art, for example in: DeWitt et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90:6909; Erb et al. (1994) Proc. Natl. Acad. Sci. USA 91:11422; Zuckermann et al. (1994). J. Med. Chem. 37:2678; Cho et al. (1993) Science 261:1303; Carrell et al. (1994) Angew. Chem. Int. Ed. Engl. 33:2059; Carell et al. (1994) Angew. Chem. Int. Ed. Engl. 33:2061; and in Gallop et al. (1994) J. Med. Chem. 37:1233.

[0265] Libraries of compounds may be presented in solution (e.g., Houghten (1992) Biotechniques 13:412-421), or on beads (Lam (1991) Nature 354:82-84), chips (Fodor (1993) Nature 364:555-556), bacteria (Ladner U.S. Pat. No. 5,223,409), spores (Ladner U.S. Pat. No. '409), plasmids (Cull et al. (1992) Proc Natl Acad Sci USA 89:1865-1869) or on phage (Scott and Smith (1990) Science 249:386-390); (Devlin (1990) Science 249:404-406); (Cwirla et al. (1990) Proc. Natl. Acad. Sci. 87:6378-6382); (Felici (1991) J. Mol. Biol. 222:301-310); (Ladner supra.).

[0266] In one embodiment, an assay is a cell-based assay in which a cell which expresses a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or biologically active portion thereof is contacted with a test compound and the ability of the test compound to modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is determined. Determining the ability of the test compound to modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity can be accomplished by monitoring, for example, intracellular calcium, IP₃, cAMP, or diacylglycerol concentration, the phosphorylation profile of intracellular proteins, cell proliferation and/or migration, gene expression of, for example, cell surface adhesion molecules or genes associated with angiogenesis, or the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-regulated transcription factor. The cell can be of mammalian origin, e.g., an endothelial cell. In one embodiment, compounds that interact with a receptor domain can be screened for their ability to function as ligands, i.e., to bind to the receptor and modulate a signal transduction pathway. Identification of ligands, and measuring the activity of the ligand-receptor complex, leads to the identification of modulators (e.g., antagonists) of this interaction. Such modulators may be useful in the treatment of cardiovascular disease.

[0267] The ability of the test compound to modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 binding to a substrate or to bind to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can also be determined. Determining the ability of the test compound to modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 binding to a substrate can be accomplished, for example, by coupling the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate with a radioisotope or enzymatic label such that binding of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be determined by detecting the labeled 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate in a complex. 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 could also be coupled with a radioisotope or enzymatic label to monitor the ability of a test compound to modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 binding to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate in a complex. Determining the ability of the test compound to bind 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be accomplished, for example, by coupling the compound with a radioisotope or enzymatic label such that binding of the compound to 1682, 6169, 6193, 7771, 14395, 29002, 33216 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be determined by detecting the labeled 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 compound in a complex. For example, compounds (e.g., 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 ligands or substrates) can be labeled with ¹²⁵I, ³⁵S, ¹⁴C, or ³H, either directly or indirectly, and the radioisotope detected by direct counting of radioemmission or by scintillation counting. Compounds can further be enzymatically labeled with, for example, horseradish peroxidase, alkaline phosphatase, or luciferase, and the enzymatic label detected by determination of conversion of an appropriate substrate to product.

[0268] It is also within the scope of this invention to determine the ability of a compound (e.g., a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 ligand or substrate) to interact with 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 without the labeling of any of the interactants. For example, a microphysiometer can be used to detect the interaction of a compound with 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 without the labeling of either the compound or the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 (McConnell, H. M. et al. (1992) Science 257:1906-1912. As used herein, a “microphysiometer” (e.g., Cytosensor) is an analytical instrument that measures the rate at which a cell acidifies its environment using a light-addressable potentiometric sensor (LAPS). Changes in this acidification rate can be used as an indicator of the interaction between a compound and 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585.

[0269] In another embodiment, an assay is a cell-based assay comprising contacting a cell expressing a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135,-10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule (e.g., a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate) with a test compound and determining the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule. Determining the ability of the test compound to modulate the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule can be accomplished, for example, by determining the ability of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to bind to or interact with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule.

[0270] Determining the ability of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or a biologically active fragment thereof, to bind to or interact with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule can be accomplished by one of the methods described above for determining direct binding. In a preferred embodiment, determining the ability of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to bind to or interact with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule can be accomplished by determining the activity of the target molecule. For example, the activity of the target molecule can be determined by detecting induction of a cellular second messenger of the target (i.e., intracellular Ca²⁺, diacylglycerol, IP₃, cAMP), detecting catalytic/enzymatic activity of the target on an appropriate substrate, detecting the induction of a reporter gene (comprising a target-responsive regulatory element operatively linked to a nucleic acid encoding a detectable marker, e.g., luciferase), or detecting a target-regulated cellular response (e.g., gene expression).

[0271] In yet another embodiment, an assay of the present invention is a cell-free assay in which a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or biologically active portion thereof, is contacted with a test compound and the ability of the test compound to bind to the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or biologically active portion thereof is determined. Preferred biologically active portions of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins to be used in assays of the present invention include fragments which participate in interactions with non-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 molecules, e.g., fragments with high surface probability scores. Binding of the test compound to the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can be determined either directly or indirectly as described above. In a preferred embodiment, the assay includes contacting the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or biologically active portion thereof with a known compound which binds 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, wherein determining the ability of the test compound to interact with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein comprises determining the ability of the test compound to preferentially bind to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 or biologically active portion thereof as compared to the known compound. Compounds that modulate the interaction of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 with a known target protein may be useful in regulating the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, especially a mutant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein.

[0272] In another embodiment, the assay is a cell-free assay in which a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or biologically active portion thereof is contacted with a test compound and the ability of the test compound to modulate (e.g., stimulate or inhibit) the activity of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or biologically active portion thereof is determined. Determining the ability of the test compound to modulate the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can be accomplished, for example, by determining the ability of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to bind to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule by one of the methods described above for determining direct binding. Determining the ability of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to bind to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule can also be accomplished using a technology such as real-time Biomolecular Interaction Analysis (BIA) (Sjolander, S. and Urbaniczky, C. (1991) Anal. Chem. 63:2338-2345 and Szabo et al. (1995) Curr. Opin. Struct. Biol. 5:699-705). As used herein, “BIA” is a technology for studying biospecific interactions in real time, without labeling any of the interactants (e.g., BIAcore). Changes in the optical phenomenon of surface plasmon resonance (SPR) can be used as an indication of real-time reactions between biological molecules.

[0273] In another embodiment, determining the ability of the test compound to modulate the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can be accomplished by determining the ability of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to further modulate the activity of a downstream effector of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule. For example, the activity of the effector molecule on an appropriate target can be determined or the binding of the effector to an appropriate target can be determined as previously described.

[0274] In yet another embodiment, the cell-free assay involves contacting a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or biologically active portion thereof with a known compound which binds the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to form an assay mixture, contacting the assay mixture with a test compound, and determining the ability of the test compound to interact with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, wherein determining the ability of the test compound to interact with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein comprises determining the ability of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to preferentially bind to or modulate the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule.

[0275] In more than one embodiment of the above assay methods of the present invention, it may be desirable to immobilize either 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 or its target molecule to facilitate separation of complexed from uncomplexed forms of one or both of the proteins, as well as to accommodate automation of the assay. Binding of a test compound to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, or interaction of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein with a target molecule in the presence and absence of a candidate compound, can be accomplished in any vessel suitable for containing the reactants. Examples of such vessels include microtitre plates, test tubes, and micro-centrifuge tubes. In one embodiment, a fusion protein can be provided which adds a domain that allows one or both of the proteins to be bound to a matrix. For example, glutathione-S-transferase/1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion proteins or glutathione-S-transferase/target fusion proteins can be adsorbed onto glutathione sepharose beads (Sigma Chemical, St. Louis, Mo.) or glutathione derivatized microtitre plates, which are then combined with the test compound or the test compound and either the non-adsorbed target protein or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, and the mixture incubated under conditions conducive to complex formation (e.g., at physiological conditions for salt and pH). Following incubation, the beads or microtitre plate wells are washed to remove any unbound components, the matrix immobilized in the case of beads, complex determined either directly or indirectly, for example, as described above. Alternatively, the complexes can be dissociated from the matrix, and the level of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 binding or activity determined using standard techniques.

[0276] Other techniques for immobilizing proteins on matrices can also be used in the screening assays of the invention. For example, either a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 target molecule can be immobilized utilizing conjugation of biotin and streptavidin. Biotinylated 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or target molecules can be prepared from biotin-NHS (N-hydroxy-succinimide) using techniques known in the art (e.g., biotinylation kit, Pierce Chemicals, Rockford, Ill.), and immobilized in the wells of streptavidin-coated 96 well plates (Pierce Chemical). Alternatively, antibodies reactive with 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or target molecules but which do not interfere with binding of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to its target molecule can be derivatized to the wells of the plate, and unbound target or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein trapped in the wells by antibody conjugation. Methods for detecting such complexes, in addition to those described above for the GST-immobilized complexes, include immunodetection of complexes using antibodies reactive with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or target molecule, as well as enzyme-linked assays which rely on detecting an enzymatic activity associated with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or target molecule.

[0277] In another embodiment, modulators of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression are identified in a method wherein a cell is contacted with a candidate compound and the expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein in the cell is determined. The level of expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein in the presence of the candidate compound is compared to the level of expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein in the absence of the candidate compound. The candidate compound can then be identified as a modulator of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression based on this comparison. For example, when expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein is greater (statistically significantly greater) in the presence of the candidate compound than in its absence, the candidate compound is identified as a stimulator of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein expression. Alternatively, when expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein is less (statistically significantly less) in the presence of the candidate compound than in its absence, the candidate compound is identified as an inhibitor of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein expression. The level of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein expression in the cells can be determined by methods described herein for detecting 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or protein.

[0278] In yet another aspect of the invention, the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins can be used as “bait proteins” in a two-hybrid assay or three-hybrid assay (see, e.g., U.S. Pat. No. 5,283,317; Zervos et al. (1993) Cell 72:223-232; Madura et al. (1993) J. Biol. Chem. 268:12046-12054; Bartel et al. (1993) Biotechniques 14:920-924; Iwabuchi et al. (1993) Oncogene 8:1693-1696; and Brent WO94/10300), to identify other proteins, which bind to or interact with 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 (“1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-binding proteins” or “1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-bp”) and are involved in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity. Such 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-binding proteins are also likely to be involved in the propagation of signals by the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 targets as, for example, downstream elements of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-mediated signaling pathway. Alternatively, such 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-binding proteins are likely to be 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 inhibitors.

[0279] The two-hybrid system is based on the modular nature of most transcription factors, which consist of separable DNA-binding and activation domains. Briefly, the assay utilizes two different DNA constructs. In one construct, the gene that codes for a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein is fused to a gene encoding the DNA binding domain of a known transcription factor (e.g., GAL-4). In the other construct, a DNA sequence, from a library of DNA sequences, that encodes an unidentified protein (“prey” or “sample”) is fused to a gene that codes for the activation domain of the known transcription factor. If the “bait” and the “prey” proteins are able to interact, in vivo, forming a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-dependent complex, the DNA-binding and activation domains of the transcription factor are brought into close proximity. This proximity allows transcription of a reporter gene (e.g., LacZ) which is operably linked to a transcriptional regulatory site responsive to the transcription factor. Expression of the reporter gene can be detected and cell colonies containing the functional transcription factor can be isolated and used to obtain the cloned gene which encodes the protein which interacts with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein.

[0280] In another aspect, the invention pertains to a combination of two or more of the assays described herein. For example, a modulating agent can be identified using a cell-based or a cell free assay, and the ability of the agent to modulate the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can be confirmed in vivo, e.g., in an animal such as an animal model for cardiovascular disease, e.g., atherosclerosis and/or thrombosis, as described herein.

[0281] This invention further pertains to novel agents identified by the above-described screening assays. Accordingly, it is within the scope of this invention to further use an agent identified as described herein in an appropriate animal model. For example, an agent identified as described herein (e.g., a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulating agent, an antisense 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecule, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-specific antibody, or a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-binding partner) can be used in an animal model to determine the efficacy, toxicity, or side effects of treatment with such an agent. Alternatively, an agent identified as described herein can be used in an animal model to determine the mechanism of action of such an agent. Furthermore, this invention pertains to uses of novel agents identified by the above-described screening assays for treatments as described herein.

[0282] Any of the compounds, including but not limited to compounds such as those identified in the foregoing assay systems, may be tested for the ability to treat cardiovascular disease symptoms. Cell-based and animal model-based assays for the identification of compounds exhibiting such an ability to ameliorate cardiovascular disease systems are described herein.

[0283] In one aspect, cell-based systems, as described herein, may be used to identify compounds which may act to treat at least one cardiovascular disease symptom. For example, such cell systems may be exposed to a compound, suspected of exhibiting an ability to treat cardiovascular disease symptoms, at a sufficient concentration and for a time sufficient to elicit such an amelioration of cardiovascular disease symptoms in the exposed cells. After exposure, the cells are examined to determine whether one or more of the cardiovascular disease cellular phenotypes has been altered to resemble a more normal or more wild type, non-cardiovascular disease phenotype. Cellular phenotypes that are associated with cardiovascular disease states include aberrant proliferation and migration, angiogenesis, deposition of extracellular matrix components, accumulation of intracellular lipids, and expression of growth factors, cytokines, and other inflammatory mediators.

[0284] In addition, animal-based cardiovascular disease systems, such as those described herein, may be used to identify compounds capable of ameliorating cardiovascular disease symptoms. Such animal models may be used as test substrates for the identification of drugs, pharmaceuticals, therapies, and interventions which may be effective in treating cardiovascular disease. For example, animal models may be exposed to a compound, suspected of exhibiting an ability to ameliorate cardiovascular disease symptoms, at a sufficient concentration and for a time sufficient to elicit such an amelioration of cardiovascular disease symptoms in the exposed animals. The response of the animals to the exposure may be monitored by assessing the reversal of disorders associated with cardiovascular disease, for example, by counting the number of atherosclerotic plaques and/or measuring their size before and after treatment.

[0285] With regard to intervention, any treatments which reverse any aspect of cardiovascular disease symptoms should be considered as candidates for human cardiovascular disease therapeutic intervention. Dosages of test agents may be determined by deriving dose-response curves.

[0286] Additionally, gene expression patterns may be utilized to assess the ability of a compound to ameliorate cardiovascular disease symptoms. For example, the expression pattern of one or more genes may form part of a “gene expression profile” or “transcriptional profile” which may be then be used in such an assessment. “Gene expression profile” or “transcriptional profile”, as used herein, includes the pattern of mRNA expression obtained for a given tissue or cell type under a given set of conditions. Such conditions may include, but are not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation, including any of the control or experimental conditions described herein, for example, atherogenic cytokine stimulation of macrophages. Gene expression profiles may be generated, for example, by utilizing a differential display procedure, Northern analysis and/or RT-PCR. In one embodiment, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences may be used as probes and/or PCR primers for the generation and corroboration of such gene expression profiles.

[0287] Gene expression profiles may be characterized for known states, either cardiovascular disease or normal, within the cell- and/or animal-based model systems. Subsequently, these known gene expression profiles may be compared to ascertain the effect a test compound has to modify such gene expression profiles, and to cause the profile to more closely resemble that of a more desirable profile.

[0288] For example, administration of a compound may cause the gene expression profile of a cardiovascular disease model system to more closely resemble the control system. Administration of a compound may, alternatively, cause the gene expression profile of a control system to begin to mimic a cardiovascular disease state. Such a compound may, for example, be used in further characterizing the compound of interest, or may be used in the generation of additional animal models.

[0289] Cell- and Animal-Based Model Systems

[0290] Described herein are cell- and animal-based systems which act as models for cardiovascular disease. These systems may be used in a variety of applications. For example, the cell- and animal-based model systems may be used to further characterize differentially expressed genes associated with cardiovascular disease, e.g., 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585. In addition, animal- and cell-based assays may be used as part of screening strategies designed to identify compounds which are capable of ameliorating cardiovascular disease symptoms, as described, below. Thus, the animal- and cell-based models may be used to identify drugs, pharmaceuticals, therapies and interventions which may be effective in treating cardiovascular disease. Furthermore, such animal models may be used to determine the LD50 and the ED50 in animal subjects, and such data can be used to determine the in vivo efficacy of potential cardiovascular disease treatments.

[0291] Animal-Based Systems

[0292] Animal-based model systems of cardiovascular disease may include, but are not limited to, non-recombinant and engineered transgenic animals.

[0293] Non-recombinant animal models for cardiovascular disease may include, for example, genetic models. Such genetic cardiovascular disease models may include, for example, ApoB or ApoR deficient pigs (Rapacz, et al., 1986, Science 234:1573-1577) and Watanabe heritable hyperlipidemic (WHHL) rabbits (Kita et al., 1987, Proc. Natl. Acad. Sci USA 84: 5928-5931). Transgenic mouse models in cardiovascular disease and angiogenesis are reviewed in Carmeliet, P. and Collen, D. (2000) J. Pathol. 190:387-405.

[0294] Non-recombinant, non-genetic animal models of atherosclerosis may include, for example, pig, rabbit, or rat models in which the animal has been exposed to either chemical wounding through dietary supplementation of LDL, or mechanical wounding through balloon catheter angioplasty. Animal models of cardiovascular disease also include rat myocardial infarction models (described in, for example, Schwarz, ER et al. (2000) J. Am. Coll. Cardiol. 35:1323-1330) and models of chromic cardiac ischemia in rabbits (described in, for example, Operschall, C et al. (2000) J. Appl. Physiol. 88:1438-1445).

[0295] Additionally, animal models exhibiting cardiovascular disease symptoms may be engineered by using, for example, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences described above, in conjunction with techniques for producing transgenic animals that are well known to those of skill in the art. For example, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences may be introduced into, and overexpressed in, the genome of the animal of interest, or, if endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences are present, they may either be overexpressed or, alternatively, be disrupted in order to underexpress or inactivate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression, such as described for the disruption of ApoE in mice (Plump et al., 1992, Cell 71: 343-353).

[0296] The host cells of the invention can also be used to produce non-human transgenic animals. For example, in one embodiment, a host cell of the invention is a fertilized oocyte or an embryonic stem cell into which 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-coding sequences have been introduced. Such host cells can then be used to create non-human transgenic animals in which exogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequences have been introduced into their genome or homologous recombinant animals in which endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequences have been altered. Such animals are useful for studying the function and/or activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 and for identifying and/or evaluating modulators of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity. As used herein, a “transgenic animal” is a non-human animal, preferably a mammal, more preferably a rodent such as a rat or mouse, in which one or more of the cells of the animal includes a transgene. Other examples of transgenic animals include non-human primates, sheep, dogs, cows, goats, chickens, amphibians, and the like. A transgene is exogenous DNA which is integrated into the genome of a cell from which a transgenic animal develops and which remains in the genome of the mature animal, thereby directing the expression of an encoded gene product in one or more cell types or tissues of the transgenic animal. As used herein, a “homologous recombinant animal” is a non-human animal, preferably a mammal, more preferably a mouse, in which an endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene has been altered by homologous recombination between the endogenous gene and an exogenous DNA molecule introduced into a cell of the animal, e.g., an embryonic cell of the animal, prior to development of the animal.

[0297] A transgenic animal used in the methods of the invention can be created by introducing a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-encoding nucleic acid into the male pronuclei of a fertilized oocyte, e.g., by microinjection, retroviral infection, and allowing the oocyte to develop in a pseudopregnant female foster animal. The 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 cDNA sequence can be introduced as a transgene into the genome of a non-human animal. Alternatively, a nonhuman homologue of a human 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, such as a mouse or rat 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, can be used as a transgene. Alternatively, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene homologue, such as another 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 family member, can be isolated based on hybridization to the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 cDNA sequences and used as a transgene. Intronic sequences and polyadenylation signals can also be included in the transgene to increase the efficiency of expression of the transgene. A tissue-specific regulatory sequence(s) can be operably linked to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 transgene to direct expression of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to particular cells. Methods for generating transgenic animals via embryo manipulation and microinjection, particularly animals such as mice, have become conventional in the art and are described, for example, in U.S. Pat. Nos. 4,736,866 and 4,870,009, both by Leder et al., U.S. Pat. No. 4,873,191 by Wagner et al. and in Hogan, B., Manipulating the Mouse Embryo, (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1986). Similar methods are used for production of other transgenic animals. A transgenic founder animal can be identified based upon the presence of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 transgene in its genome and/or expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA in tissues or cells of the animals. A transgenic founder animal can then be used to breed additional animals carrying the transgene. Moreover, transgenic animals carrying a transgene encoding a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can further be bred to other transgenic animals carrying other transgenes.

[0298] To create a homologous recombinant animal, a vector is prepared which contains at least a portion of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene into which a deletion, addition or substitution has been introduced to thereby alter, e.g., functionally disrupt, the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene. The 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene can be a human gene but more preferably, is a non-human homologue of a human 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene. For example, a rat 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene can be used to construct a homologous recombination nucleic acid molecule, e.g., a vector, suitable for altering an endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene in the mouse genome. In a preferred embodiment, the homologous recombination nucleic acid molecule is designed such that, upon homologous recombination, the endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene is functionally disrupted (i.e., no longer encodes a functional protein; also referred to as a “knock out” vector). Alternatively, the homologous recombination nucleic acid molecule can be designed such that, upon homologous recombination, the endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene is mutated or otherwise altered but still encodes functional protein (e.g., the upstream regulatory region can be altered to thereby alter the expression of the endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein). In the homologous recombination nucleic acid molecule, the altered portion of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene is flanked at its 5′ and 3′ ends by additional nucleic acid sequence of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene to allow for homologous recombination to occur between the exogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene carried by the homologous recombination nucleic acid molecule and an endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene in a-cell, e.g., an embryonic stem cell. The additional flanking 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid sequence is of sufficient length for successful homologous recombination with the endogenous gene. Typically, several kilobases of flanking DNA (both at the 5′ and 3′ ends) are included in the homologous recombination nucleic acid molecule (see, e.g., Thomas, K. R. and Capecchi, M. R. (1987) Cell 51:503 for a description of homologous recombination vectors). The homologous recombination nucleic acid molecule is introduced into a cell, e.g., an embryonic stem cell line (e.g., by electroporation) and cells in which the introduced 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene has homologously recombined with the endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene are selected (see e.g., Li, E. et al. (1992) Cell 69:915). The selected cells can then injected into a blastocyst of an animal (e.g., a mouse) to form aggregation chimeras (see e.g., Bradley, A. in Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, E. J. Robertson, ed. (IRL, Oxford, 1987) pp. 113-152). A chimeric embryo can then be implanted into a suitable pseudopregnant female foster animal and the embryo brought to term. Progeny harboring the homologously recombined DNA in their germ cells can be used to breed animals in which all cells of the animal contain the homologously recombined DNA by germline transmission of the transgene. Methods for constructing homologous recombination nucleic acid molecules, e.g., vectors, or homologous recombinant animals are described further in Bradley, A. (1991) Current Opinion in Biotechnology 2:823-829 and in PCT International Publication Nos.: WO 90/11354 by Le Mouellec et al.; WO 91/01140 by Smithies et al.; WO 92/0968 by Zijistra et al.; and WO 93/04169 by Berns et al.

[0299] In another embodiment, transgenic non-human animals for use in the methods of the invention can be produced which contain selected systems which allow for regulated expression of the transgene. One example of such a system is the cre/loxP recombinase system of bacteriophage P1. For a description of the cre/loxP recombinase system, see, e.g., Lakso et al. (1992) Proc. Natl. Acad. Sci. USA 89:6232-6236. Another example of a recombinase system is the FLP recombinase system of Saccharomyces cerevisiae (O'Gorman et al. (1991) Science 251:1351-1355. If a cre/loxP recombinase system is used to regulate expression of the transgene, animals containing transgenes encoding both the Cre recombinase and a selected protein are required. Such animals can be provided through the construction of “double” transgenic animals, e.g., by mating two transgenic animals, one containing a transgene encoding a selected protein and the other containing a transgene encoding a recombinase.

[0300] Clones of the non-human transgenic animals described herein can also be produced according to the methods described in Wilmut, I. et al. (1997) Nature 385:810-813 and PCT International Publication Nos. WO 97/07668 and WO 97/07669. In brief, a cell, e.g., a somatic cell, from the transgenic animal can be isolated and induced to exit the growth cycle and enter G_(o) phase. The quiescent cell can then be fused, e.g., through the use of electrical pulses, to an enucleated oocyte from an animal of the same species from which the quiescent cell is isolated. The reconstructed oocyte is then cultured such that it develops to morula or blastocyte and then transferred to pseudopregnant female foster animal. The offspring borne of this female foster animal will be a clone of the animal from which the cell, e.g., the somatic cell, is isolated.

[0301] The 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 transgenic animals that express 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 peptide (detected immunocytochemically, using antibodies directed against 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 epitopes) at easily detectable levels should then be further evaluated to identify those animals which display characteristic cardiovascular disease symptoms. Such cardiovascular disease symptoms may include, for example, increased prevalence and size of fatty streaks and/or cardiovascular disease plaques.

[0302] Additionally, specific cell types (e.g., endothelial cells) within the transgenic animals may be analyzed and assayed for cellular phenotypes characteristic of cardiovascular disease. In the case of endothelial cells, such phenotypes include, but are not limited to cell proliferation, migration, angiogenesis, production of proinflammatory growth factors and cytokines, and adhesion to inflammatory cells. In the case of monocytes, such phenotypes may include but are not limited to increases in rates of LDL uptake, adhesion to endothelial cells, transmigration, foam cell formation, fatty streak formation, and production of foam cell specific products. Cellular phenotypes may include a particular cell type's pattern of expression of genes associated with cardiovascular disease as compared to known expression profiles of the particular cell type in animals exhibiting cardiovascular disease symptoms.

[0303] Cell-Based Systems

[0304] Cells that contain and express 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences which encode a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, and, further, exhibit cellular phenotypes associated with cardiovascular disease, may be used to identify compounds that exhibit anti-cardiovascular disease activity. Such cells may include non-recombinant monocyte cell lines, such as U937 (ATCC# CRL-1593), THP-1 (ATCC#TIB-202), and P388D1 (ATCC# TIB-63); endothelial cells such as human umbilical vein endothelial cells (HUVECs), human microvascular endothelial cells (HMVEC), and bovine aortic endothelial cells (BAECs); as well as generic mammalian cell lines such as HeLa cells and COS cells, e.g., COS-7 (ATCC# CRL-1651). Further, such cells may include recombinant, transgenic cell lines. For example, the cardiovascular disease animal models of the invention, discussed above, may be used to generate cell lines, containing one or more cell types involved in cardiovascular disease, that can be used as cell culture models for this disorder. While primary cultures derived from the cardiovascular disease transgenic animals of the invention may be utilized, the generation of continuous cell lines is preferred. For examples of techniques which may be used to derive a continuous cell line from the transgenic animals, see Small et al., (1985) Mol. Cell Biol. 5:642-648.

[0305] Alternatively, cells of a cell type known to be involved in cardiovascular disease may be transfected with sequences capable of increasing or decreasing the amount of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression within the cell. For example, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences may be introduced into, and overexpressed in, the genome of the cell of interest, or, if endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences are present, they may be either overexpressed or, alternatively disrupted in order to underexpress or inactivate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression.

[0306] In order to overexpress a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, the coding portion of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene may be ligated to a regulatory sequence which is capable of driving gene expression in the cell type of interest, e.g., an endothelial cell. Such regulatory regions will be well known to those of skill in the art, and may be utilized in the absence of undue experimentation. Recombinant methods for expressing target genes are described above.

[0307] For underexpression of an endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequence, such a sequence may be isolated and engineered such that when reintroduced into the genome of the cell type of interest, the endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 alleles will be inactivated. Preferably, the engineered 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequence is introduced via gene targeting such that the endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequence is disrupted upon integration of the engineered 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequence into the cell's genome. Transfection of host cells with 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 5959.0, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 genes is discussed, above.

[0308] Cells treated with compounds or transfected with 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 genes can be examined for phenotypes associated with cardiovascular disease. In the case of monocytes, such phenotypes include but are not limited to increases in rates of LDL uptake, adhesion to endothelial cells, transmigration, foam cell formation, fatty streak formation, and production by foam cells of growth factors such as bFGF, IGF-I, VEGF, IL-1, M-CSF, TGFβ, TGFα, TNFα, HB-EGF, PDGF, IFN-γ, and GM-CSF. Transmigration rates, for example, may be measured using the in vitro system of Navab et al. (1988) J. Clin. Invest. 82:1853-1863, by quantifying the number of monocytes that migrate across the endothelial monolayer and into the collagen layer of the subendothelial space.

[0309] Similarly, endothelial cells can be treated with test compounds or transfected with genetically engineered 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 genes. The endothelial cells can then be examined for phenotypes associated with cardiovascular disease, including, but not limited to changes in cellular morphology, cell proliferation, cell migration, and mononuclear cell adhesion; or for the effects on production of other proteins involved in cardiovascular disease such as adhesion molecules (e.g., ICAM, VCAM, E-selectin), growth factors and cytokines (e.g., PDGF, IL-1β, TNFα, MCF), and proteins involved in angiogenesis (e.g., FLK, FLT).

[0310] Transfection of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid may be accomplished by using standard techniques (described in, for example, Ausubel (1989) supra). Transfected cells should be evaluated for the presence of the recombinant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences, for expression and accumulation of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA, and for the presence of recombinant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein production. In instances wherein a decrease in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression is desired, standard techniques may be used to demonstrate whether a decrease in endogenous 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression and/or in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein production is achieved.

[0311] Cellular models for the study of cardiovascular disease and angiogenesis include models of endothelial cell differentiation on Matrigel (Baatout, S. et al. (1996) Rom. J. Intern. Med. 34:263-269; Benelli, R et al. (1999) Int. J. Biol. Markers 14:243-246), embryonic stem cell models of vascular morphogenesis (Doetschman, T. et al. (1993) Hypertension 22:618-629), the culture of microvessel fragments in physiological gels (Hoying, J B et al. (1996) In Vitro Cell Dev. Biol. Anim. 32: 409-419; U.S. Pat. No. 5,976,782), and the treatment of endothelial cells and smooth muscle cells with atherogenic and angiogenic factors including growth factors and cytokines (e.g., IL-1β, PDGF, TNFα, VEGF), homocysteine, and LDL. In vitro angiogenesis models are described in, for example, Black, A F et al. (1999) Cell Biol. Toxicol. 15:81-90.

[0312] Predictive Medicine:

[0313] The present invention also pertains to the field of predictive medicine in which diagnostic assays, prognostic assays, and monitoring clinical trials are used for prognostic (predictive) purposes to thereby treat an individual prophylactically. Accordingly, one aspect of the present invention relates to diagnostic assays for determining 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein and/or nucleic acid expression as well as 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity, in the context of a biological sample (e.g., blood, serum, cells, e.g., endothelial cells, or tissue, e.g., vascular tissue) to thereby determine whether an individual is afflicted with a cardiovascular disease. The invention also provides for prognostic (or predictive) assays for determining whether an individual is at risk of developing a cardiovascular disorder. For example, mutations in a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene can be assayed for in a biological sample. Such assays can be used for prognostic or predictive purpose to thereby phophylactically treat an individual prior to the onset of a cardiovascular disorder, e.g., atherosclerosis.

[0314] Another aspect of the invention pertains to monitoring the influence of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulators (e.g., anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibodies or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 ribozymes) on the expression or activity of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 in clinical trials.

[0315] These and other agents are described in further detail in the following sections.

[0316] Diagnostic Assays For Cardiovascular Disease

[0317] To determine whether a subject is afflicted with a cardiovascular disease, a biological sample may be obtained from a subject and the biological sample may be contacted with a compound or an agent capable of detecting a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or nucleic acid (e.g., mRNA or genomic DNA) that encodes a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, in the biological sample. A preferred agent for detecting 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or genomic DNA is a labeled nucleic acid probe capable of hybridizing to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or genomic DNA. The nucleic acid probe can be, for example, the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid set forth in SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, or a portion thereof, such as an oligonucleotide of at least 15, 20, 25, 30, 25, 40, 45, 50, 100, 250 or 500 nucleotides in length and sufficient to specifically hybridize under stringent conditions to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA or genomic DNA. Other suitable probes for use in the diagnostic assays of the invention are described herein.

[0318] A preferred agent for detecting 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein in a sample is an antibody capable of binding to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, preferably an antibody with a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab or F(ab′)2) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently labeled streptavidin.

[0319] The term “biological sample” is intended to include tissues, cells, and biological fluids isolated from a subject, as well as tissues, cells, and fluids present within a subject. That is, the detection method of the invention can be used to detect 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA include Northern hybridizations and in situ hybridizations. In vitro techniques for detection of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations and immunofluorescence. In vitro techniques for detection of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 genomic DNA include Southern hybridizations. Furthermore, in vivo techniques for detection of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein include introducing into a subject a labeled anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques.

[0320] In another embodiment, the methods further involve obtaining a control biological sample from a control subject, contacting the control sample with a compound or agent capable of detecting 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, mRNA, or genomic DNA, such that the presence of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18, 036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, mRNA or genomic DNA is detected in the biological sample, and comparing the presence of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, mRNA or genomic DNA in the control sample with the presence of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, mRNA or genomic DNA in the test sample.

[0321] Prognostic Assays for Cardiovascular Disease

[0322] The present invention further pertains to methods for identifying subjects having or at risk of developing a cardiovascular disease associated with aberrant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity.

[0323] As used herein, the term “aberrant” includes a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity which deviates from the wild type 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity. Aberrant expression or activity includes increased or decreased expression or activity, as well as expression or activity which does not follow the wild type developmental pattern of expression or the subcellular pattern of expression. For example, aberrant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity is intended to include the cases in which a mutation in the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene causes the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene to be under-expressed or over-expressed and situations in which such mutations result in a non-functional 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or a protein which does not function in a wild-type fashion, e.g., a protein which does not interact with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate, or one which interacts with a non-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate.

[0324] The assays described herein, such as the preceding diagnostic assays or the following assays, can be used to identify a subject having or at risk of developing a cardiovascular disease, e.g., including but not limited to, atherosclerosis, ischemia/reperfusion injury, hypertension, restenosis, arterial inflammation, and endothelial cell disorders. A biological sample may be obtained from a subject and tested for the presence or absence of a genetic alteration. For example, such genetic alterations can be detected by ascertaining the existence of at least one of 1) a deletion of one or more nucleotides from a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, 2) an addition of one or more nucleotides to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, 3) a substitution of one or more nucleotides of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, 4) a chromosomal rearrangement of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, 5) an alteration in the level of a messenger RNA transcript of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, 6) aberrant modification of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, such as of the methylation pattern of the genomic DNA, 7) the presence of a non-wild type splicing pattern of a messenger RNA transcript of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, 8) a non-wild type level of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-protein, 9) allelic loss of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, and 10) inappropriate post-translational modification of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-protein.

[0325] As described herein, there are a large number of assays known in the art which can be used for detecting genetic alterations in a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene. For example, a genetic alteration in a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene may be detected using a probe/primer in a polymerase chain reaction (PCR) (see, e.g., U.S. Pat. Nos. 4,683,195 and 4,683,202), such as anchor PCR or RACE PCR, or, alternatively, in a ligation chain reaction (LCR) (see, e.g., Landegran et al. (1988) Science 241:1077-1080; and Nakazawa et al. (1994) Proc. Natl. Acad. Sci. USA 91:360-364), the latter of which can be particularly useful for detecting point mutations in a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene (see Abravaya et al. (1995) Nucleic Acids Res. 23:675-682). This method includes collecting a biological sample from a subject, isolating nucleic acid (e.g., genomic DNA, mRNA or both) from the sample, contacting the nucleic acid sample with one or more primers which specifically hybridize to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene under conditions such that hybridization and amplification of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene (if present) occurs, and detecting the presence or absence of an amplification product, or detecting the size of the amplification product and comparing the length to a control sample. It is anticipated that PCR and/or LCR may be desirable to use as a preliminary amplification step in conjunction with any of the techniques used for detecting mutations described herein.

[0326] Alternative amplification methods include: self sustained sequence replication (Guatelli, J. C. et al. (1990) Proc. Natl. Acad. Sci. USA 87:1874-1878), transcriptional amplification system (Kwoh, D. Y. et al. (1989) Proc. Natl. Acad. Sci. USA 86:1173-1177), Q-Beta Replicase (Lizardi, P. M. et al. (1988) Bio-Technology 6:1197), or any other nucleic acid amplification method, followed by the detection of the amplified molecules using techniques well known to those of skill in the art. These detection schemes are especially useful for the detection of nucleic acid molecules if such molecules are present in very low numbers.

[0327] In an alternative embodiment, mutations in a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene from a biological sample can be identified by alterations in restriction enzyme cleavage patterns. For example, sample and control DNA is isolated, amplified (optionally), digested with one or more restriction endonucleases, and fragment length sizes are determined by gel electrophoresis and compared. Differences in fragment length sizes between sample and control DNA indicates mutations in the sample DNA. Moreover, the use of sequence specific ribozymes (see, for example, U.S. Pat. No. 5,498,531) can be used to score for the presence of specific mutations by development or loss of a ribozyme cleavage site.

[0328] In other embodiments, genetic mutations in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be identified by hybridizing biological sample derived and control nucleic acids, e.g., DNA or RNA, to high density arrays containing hundreds or thousands of oligonucleotide probes (Cronin, M. T. et al. (1996) Human Mutation 7:244-255; Kozal, M. J. et al. (1996) Nature Medicine 2:753-759). For example, genetic mutations in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be identified in two dimensional arrays containing light-generated DNA probes as described in Cronin, M. T. et al. (1996) supra. Briefly, a first hybridization array of probes can be used to scan through long stretches of DNA in a sample and control to identify base changes between the sequences by making linear arrays of sequential, overlapping probes. This step allows for the identification of point mutations. This step is followed by a second hybridization array that allows for the characterization of specific mutations by using smaller, specialized probe arrays complementary to all variants or mutations detected. Each mutation array is composed of parallel probe sets, one complementary to the wild-type gene and the other complementary to the mutant gene.

[0329] In yet another embodiment, any of a variety of sequencing reactions known in the art can be used to directly sequence the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene in a biological sample and detect mutations by comparing the sequence of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 in the biological sample with the corresponding wild-type (control) sequence. Examples of sequencing reactions include those based on techniques developed by Maxam and Gilbert (1977) Proc. Natl. Acad. Sci. USA 74:560) or Sanger (1977) Proc. Natl. Acad. Sci. USA 74:5463). It is also contemplated that any of a variety of automated sequencing procedures can be utilized when performing the diagnostic assays (Naeve, C. W. (1995) Biotechniques 19:448-53), including sequencing by mass spectrometry (see, e.g., PCT International Publication No. WO 94/16101; Cohen et al. (1996) Adv. Chromatogr. 36:127-162; and Griffin et al. (1993) Appl. Biochem. Biotechnol. 38:147-159).

[0330] Other methods for detecting mutations in the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene include methods in which protection from cleavage agents is used to detect mismatched bases in RNA/RNA or RNA/DNA heteroduplexes (Myers et al. (1985) Science 230:1242). In general, the art technique of “mismatch cleavage” starts by providing heteroduplexes formed by hybridizing (labeled) RNA or DNA containing the wild-type 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequence with potentially mutant RNA or DNA obtained from a tissue sample. The double-stranded duplexes are treated with an agent which cleaves single-stranded regions of the duplex such as which will exist due to basepair mismatches between the control and sample strands. For instance, RNA/DNA duplexes can be treated with RNase and DNA/DNA hybrids treated with SI nuclease to enzymatically digest the mismatched regions. In other embodiments, either DNA/DNA or RNA/DNA duplexes can be treated with hydroxylamine or osmium tetroxide and with piperidine in order to digest mismatched regions. After digestion of the mismatched regions, the resulting material is then separated by size on denaturing polyacrylamide gels to determine the site of mutation. See, for example, Cotton et al. (1988) Proc. Natl Acad Sci USA 85:4397 and Saleeba et al. (1992) Methods Enzymol. 217:286-295. In a preferred embodiment, the control DNA or RNA can be labeled for detection.

[0331] In still another embodiment, the mismatch cleavage reaction employs one or more proteins that recognize mismatched base pairs in double-stranded DNA (so called “DNA mismatch repair” enzymes) in defined systems for detecting and mapping point mutations in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 cDNAs obtained from samples of cells. For example, the mutY enzyme of E. coli cleaves A at G/A mismatches and the thymidine DNA glycosylase from HeLa cells cleaves T at G/T mismatches (Hsu et al. (1994) Carcinogenesis 15:1657-1662). According to an exemplary embodiment, a probe based on a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequence, e.g., a wild-type 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequence, is hybridized to a cDNA or other DNA product from a test cell(s). The duplex is treated with a DNA mismatch repair enzyme, and the cleavage products, if any, can be detected from electrophoresis protocols or the like. See, for example, U.S. Pat. No. 5,459,039.

[0332] In other embodiments, alterations in electrophoretic mobility will be used to identify mutations in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 genes. For example, single strand conformation polymorphism (SSCP) may be used to detect differences in electrophoretic mobility between mutant and wild type nucleic acids (Orita et al. (1989) Proc Natl. Acad. Sci USA: 86:2766; see also Cotton (1993) Mutat. Res. 285:125-144 and Hayashi (1992) Genet. Anal. Tech. Appl. 9:73-79). Single-stranded DNA fragments of sample and control 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acids will be denatured and allowed to renature. The secondary structure of single-stranded nucleic acids varies according to sequence, the resulting alteration in electrophoretic mobility enables the detection of even a single base change. The DNA fragments may be labeled or detected with labeled probes. The sensitivity of the assay may be enhanced by using RNA (rather than DNA), in which the secondary structure is more sensitive to a change in sequence. In a preferred embodiment, the subject method utilizes heteroduplex analysis to separate double stranded heteroduplex molecules on the basis of changes in electrophoretic mobility (Keen et al. (1991) Trends Genet 7:5).

[0333] In yet another embodiment the movement of mutant or wild-type fragments in polyacrylamide gels containing a gradient of denaturant is assayed using denaturing gradient gel electrophoresis (DGGE) (Myers et al. (1985) Nature 313:495). When DGGE is used as the method of analysis, DNA will be modified to ensure that it does not completely denature, for example by adding a GC clamp of approximately 40 bp of high-melting GC-rich DNA by PCR. In a further embodiment, a temperature gradient is used in place of a denaturing gradient to identify differences in the mobility of control and sample DNA (Rosenbaum and Reissner (1987) Biophys Chem 265:12753).

[0334] Examples of other techniques for detecting point mutations include, but are not limited to, selective oligonucleotide hybridization, selective amplification, or selective primer extension. For example, oligonucleotide primers may be prepared in which the known mutation is placed centrally and then hybridized to target DNA under conditions which permit hybridization only if a perfect match is found (Saiki et al. (1986) Nature 324:163); Saiki et al. (1989) Proc. Natl Acad. Sci USA 86:6230). Such allele specific oligonucleotides are hybridized to PCR amplified target DNA or a number of different mutations when the oligonucleotides are attached to the hybridizing membrane and hybridized with labeled target DNA.

[0335] Alternatively, allele specific amplification technology which depends on selective PCR amplification may be used in conjunction with the instant invention. Oligonucleotides used as primers for specific amplification may carry the mutation of interest in the center of the molecule (so that amplification depends on differential hybridization) (Gibbs et al. (1989) Nucleic Acids Res. 17:2437-2448) or at the extreme 3′ end of one primer where, under appropriate conditions, mismatch can prevent, or reduce polymerase extension (Prossner (1993) Tibtech 11:238). In addition it may be desirable to introduce a novel restriction site in the region of the mutation to create cleavage-based detection (Gasparini et al. (1992) Mol. Cell Probes 6:1). It is anticipated that in certain embodiments amplification may also be performed using Taq ligase for amplification (Barany (1991) Proc. Natl. Acad. Sci USA 88:189). In such cases, ligation will occur only if there is a perfect match at the 3′ end of the 5′ sequence making it possible to detect the presence of a known mutation at a specific site by looking for the presence or absence of amplification.

[0336] Furthermore, the prognostic assays described herein can be used to determine whether a subject can be administered a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, or small molecule) to effectively treat a cardiovascular disease, e.g., atherosclerosis.

[0337] Monitoring of Effects During Clinical Trials

[0338] The present invention further provides methods for determining the effectiveness of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator (e.g., a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator identified herein) in treating a cardiovascular disease, e.g., atherosclerosis and/or thrombosis, in a subject. For example, the effectiveness of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator in increasing 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression, protein levels, or in upregulating 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity, can be monitored in clinical trials of subjects exhibiting decreased 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression, protein levels, or downregulated 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity. Alternatively, the effectiveness of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator in decreasing 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression, protein levels, or in downregulating 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity, can be monitored in clinical trials of subjects exhibiting increased 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression, protein levels, or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity. In such clinical trials, the expression or activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, and preferably, other genes that have been implicated in, for example, atherosclerosis and/or thrombosis can be used as a “read out” or marker of the phenotype of a particular cell, e.g., a vascular endothelial cell.

[0339] For example, and not by way of limitation, genes, including 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585, that are modulated in cells by treatment with an agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity (e.g., identified in a screening assay as described herein) can be identified. Thus, to study the effect of agents which modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity on subjects suffering from a cardiovascular disease in, for example, a clinical trial, cells can be isolated and RNA prepared and analyzed for the levels of expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 and other genes implicated in the cardiovascular disease. The levels of gene expression (e.g., a gene expression pattern) can be quantified by Northern blot analysis or RT-PCR, as described herein, or alternatively by measuring the amount of protein produced, by one of the methods described herein, or by measuring the levels of activity of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 or other genes. In this way, the gene expression pattern can serve as a marker, indicative of the physiological response of the cells to the agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity. This response state may be determined before, and at various points during treatment of the individual with the agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity.

[0340] In a preferred embodiment, the present invention provides a method for monitoring the effectiveness of treatment of a subject with an agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity (e.g., an agonist, antagonist, peptidomimetic, protein, peptide, nucleic acid, or small molecule identified by the screening assays described herein) including the steps of (i) obtaining a pre-administration sample from a subject prior to administration of the agent; (ii) detecting the level of expression of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, mRNA, or genomic DNA in the pre-administration sample; (iii) obtaining one or more post-administration samples from the subject; (iv) detecting the level of expression or activity of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, mRNA, or genomic DNA in the post-administration samples; (v) comparing the level of expression or activity of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, mRNA, or genomic DNA in the pre-administration sample with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, mRNA, or genomic DNA in the post administration sample or samples; and (vi) altering the administration of the agent to the subject accordingly. For example, increased administration of the agent may be desirable to increase the expression or activity of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 to higher levels than detected, i.e., to increase the effectiveness of the agent. Alternatively, decreased administration of the agent may be desirable to decrease expression or activity of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 to lower levels than detected, i.e. to decrease the effectiveness of the agent. According to such an embodiment, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity may be used as an indicator of the effectiveness of an agent, even in the absence of an observable phenotypic response.

[0341] Methods of Treatment of Subjects Suffering From Cardiovascular Disease:

[0342] The present invention provides for both prophylactic and therapeutic methods of treating a subject, e.g., a human, at risk of (or susceptible to) a cardiovascular disease such as atherosclerosis, ischemia/reperfusion injury, hypertension, restenosis, arterial inflammation, thrombosis, and endothelial cell disorders. With regard to both prophylactic and therapeutic methods of treatment, such treatments may be specifically tailored or modified, based on knowledge obtained from the field of pharmacogenomics. “Pharmacogenomics,” as used herein, refers to the application of genomics technologies such as gene sequencing, statistical genetics, and gene expression analysis to drugs in clinical development and on the market. More specifically, the term refers to the study of how a patient's genes determine his or her response to a drug (e.g., a patient's “drug response phenotype”, or “drug response genotype”).

[0343] Thus, another aspect of the invention provides methods for tailoring an subject's prophylactic or therapeutic treatment with either the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 molecules of the present invention or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulators according to that individual's drug response genotype. Pharmacogenomics allows a clinician or physician to target prophylactic or therapeutic treatments to patients who will most benefit from the treatment and to avoid treatment of patients who will experience toxic drug-related side effects.

[0344] Prophylactic Methods

[0345] In one aspect, the invention provides a method for preventing in a subject, a cardiovascular disease by administering to the subject an agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity, e.g., modulation of calcium influx, cellular migration, or formation of atherosclerotic lesions. Subjects at risk for a cardiovascular disease, e.g., atherosclerosis and/or thrombosis, can be identified by, for example, any or a combination of the diagnostic or prognostic assays described herein. Administration of a prophylactic agent can occur prior to the manifestation of symptoms characteristic of aberrant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity, such that a cardiovascular disease is prevented or, alternatively, delayed in its progression. Depending on the type of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 aberrancy, for example, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 agonist or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antagonist agent can be used for treating the subject. The appropriate agent can be determined based on screening assays described herein.

[0346] Therapeutic Methods

[0347] Described herein are methods and compositions whereby cardiovascular disease symptoms may be ameliorated. Certain cardiovascular diseases are brought about, at least in part, by an excessive level of a gene product, or by the presence of a gene product exhibiting an abnormal or excessive activity. As such, the reduction in the level and/or activity of such gene products would bring about the amelioration of cardiovascular disease symptoms. Techniques for the reduction of gene expression levels or the activity of a protein are discussed below.

[0348] Alternatively, certain other cardiovascular diseases are brought about, at least in part, by the absence or reduction of the level of gene expression, or a reduction in the level of a protein's activity. As such, an increase in the level of gene expression and/or the activity of such proteins would bring about the amelioration of cardiovascular disease symptoms.

[0349] In some cases, the up-regulation of a gene in a disease state reflects a protective role for that gene product in responding to the disease condition. Enhancement of such a gene's expression, or the activity of the gene product, will reinforce the protective effect it exerts. Some cardiovascular disease states may result from an abnormally low level of activity of such a protective gene. In these cases also, an increase in the level of gene expression and/or the activity of such gene products would bring about the amelioration of cardiovascular disease symptoms. Techniques for increasing target gene expression levels or target gene product activity levels are discussed herein.

[0350] Accordingly, another aspect of the invention pertains to methods of modulating 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity for therapeutic purposes. Accordingly, in an exemplary embodiment, the modulatory method of the invention involves contacting a cell with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 or agent that modulates one or more of the activities of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein activity associated with the cell (e.g., an endothelial cell or an ovarian cell). An agent that modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein activity can be an agent as described herein, such as a nucleic acid or a protein, a naturally-occurring target molecule of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein (e.g., a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 ligand or substrate), a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibody, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 agonist or antagonist, a peptidomimetic of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 agonist or antagonist, or other small molecule. In one embodiment, the agent stimulates one or more 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activities. Examples of such stimulatory agents include active 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein and a nucleic acid molecule encoding 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 that has been introduced into the cell. In another embodiment, the agent inhibits one or more 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252,<9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activities. Examples of such inhibitory agents include antisense 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecules, anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibodies, and 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 inhibitors. These modulatory methods can be performed in vitro (e.g., by culturing the cell with the agent) or, alternatively, in vivo (e.g., by administering the agent to a subject). As such, the present invention provides methods of treating an individual afflicted with a disease or disorder characterized by aberrant or unwanted expression or activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or nucleic acid molecule. In one embodiment, the method involves administering an agent (e.g., an agent identified by a screening assay described herein), or combination of agents that modulates (e.g., upregulates or downregulates) 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity. In another embodiment, the method involves administering a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or nucleic acid molecule as therapy to compensate for reduced, aberrant, or unwanted 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity.

[0351] Stimulation of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is desirable in situations in which 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 is abnormally downregulated and/or in which increased 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is likely to have a beneficial effect. Likewise, inhibition of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is desirable in situations in which 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 is abnormally upregulated and/or in which decreased 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is likely to have a beneficial effect.

[0352] Methods for Inhibiting Target Gene Expression, Synthesis, or Activity

[0353] As discussed above, genes involved in cardiovascular disorders may cause such disorders via an increased level of gene activity. In some cases, such up-regulation may have a causative or exacerbating effect on the disease state. A variety of techniques may be used to inhibit the expression, synthesis, or activity of such genes and/or proteins.

[0354] For example, compounds such as those identified through assays described above, which exhibit inhibitory activity, may be used in accordance with the invention to ameliorate cardiovascular disease symptoms. Such molecules may include, but are not limited to, small organic molecules, peptides, antibodies, and the like.

[0355] For example, compounds can be administered that compete with endogenous ligand for the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. The resulting reduction in the amount of ligand-bound 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein will modulate endothelial cell physiology. Compounds that can be particularly useful for this purpose include, for example, soluble proteins or peptides, such as peptides comprising one or more of the extracellular domains, or portions and/or analogs thereof, of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, including, for example, soluble fusion proteins such as Ig-tailed fusion proteins. (For a discussion of the production of Ig-tailed fusion proteins, see, for example, U.S. Pat. No. 5,116,964). Alternatively, compounds, such as ligand analogs or antibodies, that bind to the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 receptor site, but do not activate the protein, (e.g., receptor-ligand antagonists) can be effective in inhibiting 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein activity.

[0356] Further, antisense and ribozyme molecules which inhibit expression of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene may also be used in accordance with the invention to inhibit aberrant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene activity. Still further, triple helix molecules may be utilized in inhibiting aberrant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene activity.

[0357] The antisense nucleic acid molecules used in the methods of the invention are typically administered to a subject or generated in situ such that they hybridize with or bind to cellular mRNA and/or genomic DNA encoding a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein to thereby inhibit expression of the protein, e.g., by inhibiting transcription and/or translation. The hybridization can be by conventional nucleotide complementarity to form a stable duplex, or, for example, in the case of an antisense nucleic acid molecule which binds to DNA duplexes, through specific interactions in the major groove of the double helix. An example of a route of administration of antisense nucleic acid molecules of the invention include direct injection at a tissue site. Alternatively, antisense nucleic acid molecules can be modified to target selected cells and then administered systemically. For example, for systemic administration, antisense molecules can be modified such that they specifically bind to receptors or antigens expressed on a selected cell surface, e.g., by linking the antisense nucleic acid molecules to peptides or antibodies which bind to cell surface receptors or antigens. The antisense nucleic acid molecules can also be delivered to cells using the vectors described herein. To achieve sufficient intracellular concentrations of the antisense molecules, vector constructs in which the antisense nucleic acid molecule is placed under the control of a strong pol II or pol III promoter are preferred.

[0358] In yet another embodiment, an antisense nucleic acid molecule used in the methods of the invention is an α-anomeric nucleic acid molecule. An α-anomeric nucleic acid molecule forms specific double-stranded hybrids with complementary RNA in which, contrary to the usual β-units, the strands run parallel to each other (Gaultier et al. (1987) Nucleic Acids. Res. 15:6625-6641). The antisense nucleic acid molecule can also comprise a 2′-o-methylribonucleotide (Inoue et al. (1987) Nucleic Acids Res. 15:6131-6148) or a chimeric RNA-DNA analogue (Inoue et al. (1987) FEBS Lett. 215:327-330).

[0359] In still another embodiment, an antisense nucleic acid used in the methods of the invention is a ribozyme. Ribozymes are catalytic RNA molecules with ribonuclease activity which are capable of cleaving a single-stranded nucleic acid, such as an mRNA, to which they have a complementary region. Thus, ribozymes (e.g., hammerhead ribozymes (described in Haselhoff and Gerlach (1988) Nature 334:585-591)) can be used to catalytically cleave 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA transcripts to thereby inhibit translation of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA. A ribozyme having specificity for a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-encoding nucleic acid can be designed based upon the nucleotide sequence of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 cDNA disclosed herein (i.e., SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125.) For example, a derivative of a Tetrahymena L-19 IVS RNA can be constructed in which the nucleotide sequence of the active site is complementary to the nucleotide sequence to be cleaved in a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-encoding mRNA (see, for example, Cech et al. U.S. Pat. No. 4,987,071; and Cech et al. U.S. Pat. No. 5,116,742). Alternatively, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA can be used to select a catalytic RNA having a specific ribonuclease activity from a pool of RNA molecules (see, for example, Bartel, D. and Szostak, J. W. (1993) Science 261:1411-1418).

[0360] 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression can also be inhibited by targeting nucleotide sequences complementary to the regulatory region of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 (e.g., the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 promoter and/or enhancers) to form triple helical structures that prevent transcription of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene in target cells (see, for example, Helene, C. (1991) Anticancer Drug Des. 6(6):569-84; Helene, C. et al. (1992) Ann. N.Y. Acad. Sci. 660:27-36; and Maher, L. J. (1992) Bioassays 14(12):807-15).

[0361] Antibodies that are both specific for the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein and interfere with its activity may also be used to modulate or inhibit 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein function. Such antibodies may be generated using standard techniques described herein, against the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein itself or against peptides corresponding to portions of the protein. Such antibodies include but are not limited to polyclonal, monoclonal, Fab fragments, single chain antibodies, or chimeric antibodies.

[0362] In instances where the target gene protein is intracellular and whole antibodies are used, internalizing antibodies may be preferred. Lipofectin liposomes may be used to deliver the antibody or a fragment of the Fab region which binds to the target epitope into cells. Where fragments of the antibody are used, the smallest inhibitory

[0363] fragment which binds to the target protein's binding domain is preferred. For example, peptides having an amino acid sequence corresponding to the domain of the variable region of the antibody that binds to the target gene protein may be used. Such peptides may be synthesized chemically or produced via recombinant DNA technology using

[0364] methods well known in the art (described in, for example, Creighton (1983), supra; and Sambrook et al. (1989) supra). Single chain neutralizing antibodies which bind to intracellular target gene epitopes may also be administered. Such single chain antibodies may be administered, for example, by expressing nucleotide sequences encoding single-chain antibodies within the target cell population by utilizing, for example, techniques such as those described in Marasco et al. (1993) Proc. Natl. Acad. Sci. USA 90:7889-7893).

[0365] In some instances, the target gene protein is extracellular, or is a transmembrane protein, such as the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Antibodies that are specific for one or more extracellular domains of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, for example, and that interfere with its activity, are particularly useful in treating cardiovascular disease. Such antibodies are especially efficient because they can access the target domains directly from the bloodstream. Any of the administration techniques described below which are appropriate for peptide administration may be utilized to effectively administer inhibitory target gene antibodies to their site of action.

[0366] Methods for Restoring or Enhancing Target Gene Activity

[0367] Genes that cause cardiovascular disease may be underexpressed within cardiovascular disease situations. Alternatively, the activity of the protein products of such genes may be decreased, leading to the development of cardiovascular disease symptoms. Such down-regulation of gene expression or decrease of protein activity might have a causative or exacerbating effect on the disease state.

[0368] In some cases, genes that are up-regulated in the disease state might be exerting a protective effect. A variety of techniques may be used to increase the expression, synthesis, or activity of genes and/or proteins that exert a protective effect in response to cardiovascular disease conditions.

[0369] Described in this section are methods whereby the level 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity may be increased to levels wherein cardiovascular disease symptoms are ameliorated. The level of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity may be increased, for example, by either increasing the level of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene expression or by increasing the level of active 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein which is present.

[0370] For example, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, at a level sufficient to ameliorate cardiovascular disease symptoms may be administered to a patient exhibiting such symptoms. Any of the techniques discussed below may be used for such administration. One of skill in the art will readily know how to determine the concentration of effective, non-toxic doses of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, utilizing techniques such as those described below.

[0371] Additionally, RNA sequences encoding a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein may be directly administered to a patient exhibiting cardiovascular disease symptoms, at a concentration sufficient to produce a level of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein such that cardiovascular disease symptoms are ameliorated. Any of the techniques discussed below, which achieve intracellular administration of compounds, such as, for example, liposome administration, may be used for the administration of such RNA molecules. The RNA molecules may be produced, for example, by recombinant techniques such as those described herein.

[0372] Further, subjects may be treated by gene replacement therapy. One or more copies of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene, or a portion thereof, that directs the production of a normal 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein with 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 function, may be inserted into cells using vectors which include, but are not limited to adenovirus, adeno-associated virus, and retrovirus vectors, in addition to other particles that introduce DNA into cells, such as liposomes. Additionally, techniques such as those described above may be used for the introduction of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene sequences into human cells.

[0373] Cells, preferably, autologous cells, containing 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expressing gene sequences may then be introduced or reintroduced into the subject at positions which allow for the amelioration of cardiovascular disease symptoms. Such cell replacement techniques may be preferred, for example, when the gene product is a secreted, extracellular gene product.

[0374] Pharmaceutical Compositions

[0375] Another aspect of the invention pertains to methods for treating a subject suffering from a cardiovascular disease, e.g., atherosclerosis. These methods involve administering to a subject an agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity (e.g., an agent identified by a screening assay described herein), or a combination of such agents. In another embodiment, the method involves administering to a subject a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or nucleic acid molecule as therapy to compensate for reduced, aberrant, or unwanted 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 expression or activity.

[0376] Stimulation of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is desirable in situations in which 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 is abnormally downregulated and/or in which increased 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is likely to have a beneficial effect. Likewise, inhibition of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is desirable in situations in which 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 is abnormally upregulated and/or in which decreased 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity is likely to have a beneficial effect, e.g., inhibition of atherosclerotic lesion formation.

[0377] The agents which modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity can be administered to a subject using pharmaceutical compositions suitable for such administration. Such compositions typically comprise the agent (e.g., nucleic acid molecule, protein, or antibody) and a pharmaceutically acceptable carrier. As used herein the language “pharmaceutically acceptable carrier” is intended to include any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like, compatible with pharmaceutical administration. The use of such media and agents for pharmaceutically active substances is well known in the art. Except insofar as any conventional media or agent is incompatible with the active compound, use thereof in the compositions is contemplated. Supplementary active compounds can also be incorporated into the compositions.

[0378] A pharmaceutical composition used in the therapeutic methods of the invention is formulated to be compatible with its intended route of administration. Examples of routes of administration include parenteral, e.g., intravenous, intradermal, subcutaneous, oral (e.g., inhalation), transdermal (topical), transmucosal, and rectal administration. Solutions or suspensions used for parenteral, intradermal, or subcutaneous application can include the following components: a sterile diluent such as water for injection, saline solution, fixed oils, polyethylene glycols, glycerine, propylene glycol or other synthetic solvents; antibacterial agents such as benzyl alcohol or methyl parabens; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates or phosphates and agents for the adjustment of tonicity such as sodium chloride or dextrose. pH can be adjusted with acids or bases, such as hydrochloric acid or sodium hydroxide. The parenteral preparation can be enclosed in ampoules, disposable syringes or multiple dose vials made of glass or plastic.

[0379] Pharmaceutical compositions suitable for injectable use include sterile aqueous solutions (where water soluble) or dispersions and sterile powders for the extemporaneous preparation of sterile injectable solutions or dispersion. For intravenous administration, suitable carriers include physiological saline, bacteriostatic water, Cremophor EL™ (BASF, Parsippany, N.J.) or phosphate buffered saline (PBS). In all cases, the composition must be sterile and should be fluid to the extent that easy syringability exists. It must be stable under the conditions of manufacture and storage and must be preserved against the contaminating action of microorganisms such as bacteria and fungi. The carrier can be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyetheylene glycol, and the like), and suitable mixtures thereof. The proper fluidity can be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants. Prevention of the action of microorganisms can be achieved by various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, ascorbic acid, thimerosal, and the like. In many cases, it will be preferable to include isotonic agents, for example, sugars, polyalcohols such as manitol, sorbitol, and sodium chloride in the composition. Prolonged absorption of the injectable compositions can be brought about by including in the composition an agent which delays absorption, for example, aluminum monostearate and gelatin.

[0380] Sterile injectable solutions can be prepared by incorporating the agent that modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity (e.g., a fragment of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or an anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibody) in the required amount in an appropriate solvent with one or a combination of ingredients enumerated above, as required, followed by filtered sterilization. Generally, dispersions are prepared by incorporating the active compound into a sterile vehicle which contains a basic dispersion medium and the required other ingredients from those enumerated above. In the case of sterile powders for the preparation of sterile injectable solutions, the preferred methods of preparation are vacuum drying and freeze-drying which yields a powder of the active ingredient plus any additional desired ingredient from a previously sterile-filtered solution thereof.

[0381] Oral compositions generally include an inert diluent or an edible carrier. They can be enclosed in gelatin capsules or compressed into tablets. For the purpose of oral therapeutic administration, the active compound can be incorporated with excipients and used in the form of tablets, troches, or capsules. Oral compositions can also be prepared using a fluid carrier for use as a mouthwash, wherein the compound in the fluid carrier is applied orally and swished and expectorated or swallowed. Pharmaceutically compatible binding agents, and/or adjuvant materials can be included as part of the composition. The tablets, pills, capsules, troches and the like can contain any of the following ingredients, or compounds of a similar nature: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel, or corn starch; a lubricant such as magnesium stearate or Sterotes; a glidant such as colloidal silicon dioxide; a sweetening agent such as sucrose or saccharin; or a flavoring agent such as peppermint, methyl salicylate, or orange flavoring.

[0382] For administration by inhalation, the compounds are delivered in the form of an aerosol spray from pressured container or dispenser which contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer.

[0383] Systemic administration can also be by transmucosal or transdermal means. For transmucosal or transdermal administration, penetrants appropriate to the barrier to be permeated are used in the formulation. Such penetrants are generally known in the art, and include, for example, for transmucosal administration, detergents, bile salts, and fusidic acid derivatives. Transmucosal administration can be accomplished through the use of nasal sprays or suppositories. For transdermal administration, the active compounds are formulated into ointments, salves, gels, or creams as generally known in the art.

[0384] The agents that modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity can also be prepared in the form of suppositories (e.g., with conventional suppository bases such as cocoa butter and other glycerides) or retention enemas for rectal delivery.

[0385] In one embodiment, the agents that modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity are prepared with carriers that will protect the compound against rapid elimination from the body, such as a controlled release formulation, including implants and microencapsulated delivery systems. Biodegradable, biocompatible polymers can be used, such as ethylene vinyl acetate, polyanhydrides, polyglycolic acid, collagen, polyorthoesters, and polylactic acid. Methods for preparation of such formulations will be apparent to those skilled in the art. The materials can also be obtained commercially from Alza Corporation and Nova Pharmaceuticals, Inc. Liposomal suspensions (including liposomes targeted to infected cells with monoclonal antibodies to viral antigens) can also be used as pharmaceutically acceptable carriers. These can be prepared according to methods known to those skilled in the art, for example, as described in U.S. Pat. No. 4,522,811.

[0386] It is especially advantageous to formulate oral or parenteral compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the subject to be treated; each unit containing a predetermined quantity of active compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical carrier. The specification for the dosage unit forms of the invention are dictated by and directly dependent on the unique characteristics of the agent that modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity and the particular therapeutic effect to be achieved, and the limitations inherent in the art of compounding such an agent for the treatment of subjects.

[0387] Toxicity and therapeutic efficacy of such agents can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., for determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dose ratio between toxic and therapeutic effects is the therapeutic index and can be expressed as the ratio LD50/ED50. Agents which exhibit large therapeutic indices are preferred. While agents that exhibit toxic side effects may be used, care should be taken to design a delivery system that targets such agents to the site of affected tissue in order to minimize potential damage to uninfected cells and, thereby, reduce side effects.

[0388] The data obtained from the cell culture assays and animal studies can be used in formulating a range of dosage for use in humans. The dosage of such 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulating agents lies preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage may vary within this range depending upon the dosage form employed and the route of administration utilized. For any agent used in the therapeutic methods of the invention, the therapeutically effective dose can be estimated initially from cell culture assays. A dose may be formulated in animal models to achieve a circulating plasma concentration range that includes the IC50 (i.e., the concentration of the test compound which achieves a half-maximal inhibition of symptoms) as determined in cell culture. Such information can be used to more accurately determine useful doses in humans. Levels in plasma may be measured, for example, by high performance liquid chromatography.

[0389] As defined herein, a therapeutically effective amount of protein or polypeptide (i.e., an effective dosage) ranges from about 0.001 to 30 mg/kg body weight, preferably about 0.01 to 25 mg/kg body weight, more preferably about 0. 1 to 20 mg/kg body weight, and even more preferably about 1 to 10 mg/kg, 2 to 9 mg/kg, 3 to 8 mg/kg, 4 to 7 mg/kg, or 5 to 6 mg/kg body weight. The skilled artisan will appreciate that certain factors may influence the dosage required to effectively treat a subject, including but not limited to the severity of the disease or disorder, previous treatments, the general health and/or age of the subject, and other diseases present. Moreover, treatment of a subject with a therapeutically effective amount of a protein, polypeptide, or antibody can include a single treatment or, preferably, can include a series of treatments.

[0390] In a preferred example, a subject is treated with antibody, protein, or polypeptide in the range of between about 0.1 to 20 mg/kg body weight, one time per week for between about 1 to 10 weeks, preferably between 2 to 8 weeks, more preferably between about 3 to 7 weeks, and even more preferably for about 4, 5, or 6 weeks. It will also be appreciated that the effective dosage of antibody, protein, or polypeptide used for treatment may increase or decrease over the course of a particular treatment. Changes in dosage may result and become apparent from the results of diagnostic assays as described herein.

[0391] The present invention encompasses agents which modulate expression or activity. An agent may, for example, be a small molecule. For example, such small molecules include, but are not limited to, peptides, peptidomimetics, amino acids, amino acid analogs, polynucleotides, polynucleotide analogs, nucleotides, nucleotide analogs, organic or inorganic compounds (i.e,. including heteroorganic and organometallic compounds) having a molecular weight less than about 10,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 5,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 1,000 grams per mole, organic or inorganic compounds having a molecular weight less than about 500 grams per mole, and salts, esters, and other pharmaceutically acceptable forms of such compounds. It is understood that appropriate doses of small molecule agents depends upon a number of factors within the ken of the ordinarily skilled physician, veterinarian, or researcher. The dose(s) of the small molecule will vary, for example, depending upon the identity, size, and condition of the subject or sample being treated, further depending upon the route by which the composition is to be administered, if applicable, and the effect which the practitioner desires the small molecule to have upon the nucleic acid or polypeptide of the invention.

[0392] Exemplary doses include milligram or microgram amounts of the small molecule per kilogram of subject or sample weight (e.g., about 1 microgram per kilogram to about 500 milligrams per kilogram, about 100 micrograms per kilogram to about 5 milligrams per kilogram, or about 1 microgram per kilogram to about 50 micrograms per kilogram). It is

[0393] Furthermore understood that appropriate doses of a small molecule depend upon the potency of the small molecule with respect to the expression or activity to be modulated. Such appropriate doses may be determined using the assays described herein. When one or more of these small molecules is to be administered to an animal (e.g., a human) in order to modulate expression or activity of a polypeptide or nucleic acid of the invention, a physician, veterinarian, or researcher may, for example, prescribe a relatively low dose at first, subsequently increasing the dose until an appropriate response is obtained. In addition, it is understood that the specific dose level for any particular animal subject will depend upon a variety of factors including the activity of the specific compound employed, the age, body weight, general health, gender, and diet of the subject, the time of administration, the route of administration, the rate of excretion, any drug combination, and the degree of expression or activity to be modulated.

[0394] Further, an antibody (or fragment thereof) may be conjugated to a therapeutic moiety such as a cytotoxin, a therapeutic agent or a radioactive metal ion. A cytotoxin or cytotoxic agent includes any agent that is detrimental to cells. Examples include taxol, cytochalasin B, gramicidin D, ethidium bromide, emetine, mitomycin, etoposide, tenoposide, vincristine, vinblastine, colchicin, doxorubicin, daunorubicin, dihydroxy anthracin dione, mitoxantrone, mithramycin, actinomycin D, 1-dehydrotestosterone, glucocorticoids, procaine, tetracaine, lidocaine, propranolol, and puromycin and analogs or homologs thereof. Therapeutic agents include, but are not limited to, antimetabolites (e.g., methotrexate, 6-mercaptopurine, 6-thioguanine, cytarabine, 5-fluorouraci1 decarbazine), alkylating agents (e.g., mechlorethamine, thioepa chlorambucil, melphalan, carmustine (BSNU) and lomustine (CCNU), cyclothosphamide, busulfan, dibromomannitol, streptozotocin, mitomycin C, and cis-dichlorodiamine platinum (II) (DDP) cisplatin), anthracyclines (e.g., daunorubicin (formerly daunomycin) and doxorubicin), antibiotics (e.g., dactinomycin (formerly actinomycin), bleomycin, mithramycin, and anthramycin (AMC)), and anti-mitotic agents (e.g., vincristine and vinblastine).

[0395] The conjugates of the invention can be used for modifying a given biological response, the drug moiety is not to be construed as limited to classical chemical therapeutic agents. For example, the drug moiety may be a protein or polypeptide possessing a desired biological activity. Such proteins may include, for example, a toxin such as abrin, ricin A, pseudomonas exotoxin, or diphtheria toxin; a protein such as tumor necrosis factor, alpha-interferon, beta-interferon, nerve growth factor, platelet derived growth factor, tissue plasminogen activator; or biological response modifiers such as, for example, lymphokines, interleukin-1 (“IL-1”), interleukin-2 (“IL-2”), interleukin-6 (“IL-6”), granulocyte macrophase colony stimulating factor (“GM-CSF”), granulocyte colony stimulating factor (“G-CSF”), or other growth factors.

[0396] Techniques for conjugating such therapeutic moiety to antibodies are well known, see, e.g., Arnon et al., “Monoclonal Antibodies For Immunotargeting Of Drugs In Cancer Therapy”, in Monoclonal Antibodies And Cancer Therapy, Reisfeld et al. (eds.), pp. 243-56 (Alan R. Liss, Inc. 1985); Hellstrom et al., “Antibodies For Drug Delivery”, in Controlled Drug Delivery (2nd Ed.), Robinson et al. (eds.), pp. 623-53 (Marcel Dekker, Inc. 1987); Thorpe, “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review”, in Monoclonal Antibodies '84: Biological And Clinical Applications, Pinchera et al. (eds.), pp. 475-506 (1985); “Analysis, Results, And Future Prospective Of The Therapeutic Use Of Radiolabeled Antibody In Cancer Therapy”, in Monoclonal Antibodies For Cancer Detection And Therapy, Baldwin et al. (eds.), pp. 303-16 (Academic Press 1985), and Thorpe et al., “The Preparation And Cytotoxic Properties Of Antibody-Toxin Conjugates”, Immunol. Rev., 62:119-58 (1982). Alternatively, an antibody can be conjugated to a second antibody to form an antibody heteroconjugate as described by Segal in U.S. Pat. No. 4,676,980.

[0397] The nucleic acid molecules used in the methods of the invention can be inserted into vectors and used as gene therapy vectors. Gene therapy vectors can be delivered to a subject by, for example, intravenous injection, local administration (see U.S. Pat. No. 5,328,470) or by stereotactic injection (see, e.g., Chen et al. (1994) Proc. Natl. Acad. Sci. USA 91:3054-3057). The pharmaceutical preparation of the gene therapy vector can include the gene therapy vector in an acceptable diluent, or can comprise a slow release matrix in which the gene delivery vehicle is imbedded. Alternatively, where the complete gene delivery vector can be produced intact from recombinant cells, e.g., retroviral vectors, the pharmaceutical preparation can include one or more cells which produce the gene delivery system.

[0398] Pharmacogenomics

[0399] In conjunction with the therapeutic methods of the invention, pharmacogenomics (i.e., the study of the relationship between a subject's genotype and that subject's response to a foreign compound or drug) may be considered. Differences in metabolism of therapeutics can lead to severe toxicity or therapeutic failure by altering the relation between dose and blood concentration of the pharmacologically active drug. Thus, a physician or clinician may consider applying knowledge obtained in relevant pharmacogenomics studies in determining whether to administer an agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity, as well as tailoring the dosage and/or therapeutic regimen of treatment with an agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity.

[0400] Pharmacogenomics deals with clinically significant hereditary variations in the response to drugs due to altered drug disposition and abnormal action in affected persons. See, for example, Eichelbaum, M. et al. (1996) Clin. Exp. Pharmacol. Physiol. 23(10-11): 983-985 and Linder, M. W. et al. (1997) Clin. Chem. 43(2):254-266. In general, two types of pharmacogenetic conditions can be differentiated. Genetic conditions transmitted as a single factor altering the way drugs act on the body (altered drug action) or genetic conditions transmitted as single factors altering the way the body acts on drugs (altered drug metabolism). These pharmacogenetic conditions can occur either as rare genetic defects or as naturally-occurring polymorphisms. For example, glucose-6-phosphate aminopeptidase deficiency (G6PD) is a common inherited enzylmopathy in which the main clinical complication is haemolysis after ingestion of oxidant drugs (anti-malarials, sulfonamides, analgesics, nitrofurans) and consumption of fava beans.

[0401] One pharmacogenomics approach to identifying genes that predict drug response, known as “a genome-wide association”, relies primarily on a high-resolution map of the human genome consisting of already known gene-related markers (e.g., a “bi-allelic” gene marker map which consists of 60,000-100,000 polymorphic or variable sites on the human genome, each of which has two variants). Such a high-resolution genetic map can be compared to a map of the genome of each of a statistically significant number of patients taking part in a Phase II/III drug trial to identify markers associated with a particular observed drug response or side effect. Alternatively, such a high resolution map can be generated from a combination of some ten million known single nucleotide polymorphisms (SNPs) in the human genome. As used herein, a “SNP” is a common alteration that occurs in a single nucleotide base in a stretch of DNA. For example, a SNP may occur once per every 1000 bases of DNA. A SNP may be involved in a disease process, however, the vast majority may not be disease-associated. Given a genetic map based on the occurrence of such SNPs, individuals can be grouped into genetic categories depending on a particular pattern of SNPs in their individual genome. In such a manner, treatment regimens can be tailored to groups of genetically similar individuals, taking into account traits that may be common among such genetically similar individuals.

[0402] Alternatively, a method termed the “candidate gene approach” can be utilized to identify genes that predict drug response. According to this method, if a gene that encodes a drug target is known (e.g., a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein used in the methods of the present invention), all common variants of that gene can be fairly easily identified in the population and it can be determined if having one version of the gene versus another is associated with a particular drug response.

[0403] As an illustrative embodiment, the activity of drug metabolizing enzymes is a major determinant of both the intensity and duration of drug action. The discovery of genetic polymorphisms of drug metabolizing enzymes (e.g., N-acetyltransferase 2 (NAT 2) and the cytochrome P450 enzymes CYP2D6 and CYP2C 19) has provided an explanation as to why some patients do not obtain the expected drug effects or show exaggerated drug response and serious toxicity after taking the standard and safe dose of a drug. These polymorphisms are expressed in two phenotypes in the population, the extensive metabolizer (EM) and poor metabolizer (PM). The prevalence of PM is different among different populations. For example, the gene coding for CYP2D6 is highly polymorphic and several mutations have been identified in PM, which all lead to the absence of functional CYP2D6. Poor metabolizers of CYP2D6 and CYP2C19 quite frequently experience exaggerated drug response and side effects when they receive standard doses. If a metabolite is the active therapeutic moiety, PM show no therapeutic response, as demonstrated for the analgesic effect of codeine mediated by its CYP2D6-formed metabolite morphine. The other extreme are the so called ultra-rapid metabolizers who do not respond to standard doses. Recently, the molecular basis of ultra-rapid metabolism has been identified to be due to CYP2D6 gene amplification.

[0404] Alternatively, a method termed the “gene expression profiling” can be utilized to identify genes that predict drug response. For example, the gene expression of an animal dosed with a drug (e.g., a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 molecule or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator used in the methods of the present invention) can give an indication whether gene pathways related to toxicity have been turned on.

[0405] Information generated from more than one of the above pharmacogenomics approaches can be used to determine appropriate dosage and treatment regimens for prophylactic or therapeutic treatment of a subject. This knowledge, when applied to dosing or drug selection, can avoid adverse reactions or therapeutic failure and, thus, enhance therapeutic or prophylactic efficiency when treating a subject suffering from a cardiovascular disease, e.g., atherosclerosis, with an agent which modulates 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity.

[0406] Recombinant Expression Vectors and Host Cells Used in the Methods of the Invention

[0407] The methods of the invention (e.g., the screening assays described herein) include the use of vectors, preferably expression vectors, containing a nucleic acid encoding a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein (or a portion thereof). As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting another nucleic acid to which it has been linked. One type of vector is a “plasmid”, which refers to a circular double stranded DNA loop into which additional DNA segments can be ligated. Another type of vector is a viral vector, wherein additional DNA segments can be ligated into the viral genome. Certain vectors are capable of autonomous replication in a host cell into which they are introduced (e.g., bacterial vectors having a bacterial origin of replication and episomal mammalian vectors). Other vectors (e.g., non-episomal mammalian vectors) are integrated into the genome of a host cell upon introduction into the host cell, and thereby are replicated along with the host genome. Moreover, certain vectors are capable of directing the expression of genes to which they are operatively linked. Such vectors are referred to herein as “expression vectors”. In general, expression vectors of utility in recombinant DNA techniques are often in the form of plasmids. In the present specification, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the invention is intended to include such other forms of expression vectors, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions.

[0408] The recombinant expression vectors to be used in the methods of the invention comprise a nucleic acid of the invention in a form suitable for expression of the nucleic acid in a host cell, which means that the recombinant expression vectors include one or more regulatory sequences, selected on the basis of the host cells to be used for expression, which is operatively linked to the nucleic acid sequence to be expressed. Within a recombinant expression vector, “operably linked” is intended to mean that the nucleotide sequence of interest is linked to the regulatory sequence(s) in a manner which allows for expression of the nucleotide sequence (e.g., in an in vitro transcription/translation system or in a host cell when the vector is introduced into the host cell). The term “regulatory sequence” is intended to include promoters, enhancers and other expression control elements (e.g., polyadenylation signals). Such regulatory sequences are described, for example, in Goeddel (1990) Methods Enzymol. 185:3-7. Regulatory sequences include those which direct constitutive expression of a nucleotide sequence in many types of host cells and those which direct expression of the nucleotide sequence only in certain host cells (e.g., tissue-specific regulatory sequences). It will be appreciated by those skilled in the art that the design of the expression vector can depend on such factors as the choice of the host cell to be transformed, the level of expression of protein desired, and the like. The expression vectors of the invention can be introduced into host cells to thereby produce proteins or peptides, including fusion proteins or peptides, encoded by nucleic acids as described herein (e.g., 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins, mutant forms of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins, fusion proteins, and the like).

[0409] The recombinant expression vectors to be used in the methods of the invention can be designed for expression of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins in prokaryotic or eukaryotic cells. For example, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins can be expressed in bacterial cells such as E. coli, insect cells (using baculovirus expression vectors), yeast cells, or mammalian cells. Suitable host cells are discussed further in Goeddel (1990) supra. Alternatively, the recombinant expression vector can be transcribed and translated in vitro, for example using T7 promoter regulatory sequences and T7 polymerase.

[0410] Expression of proteins in prokaryotes is most often carried out in E. Coli with vectors containing constitutive or inducible promoters directing the expression of either fusion or non-fusion proteins. Fusion vectors add a number of amino acids to a protein encoded therein, usually to the amino terminus of the recombinant protein. Such fusion vectors typically serve three purposes: 1) to increase expression of recombinant protein; 2) to increase the solubility of the recombinant protein; and 3) to aid in the purification of the recombinant protein by acting as a ligand in affinity purification. Often, in fusion expression vectors, a proteolytic cleavage site is introduced at the junction of the fusion moiety and the recombinant protein to enable separation of the recombinant protein from the fusion moiety subsequent to purification of the fusion protein. Such enzymes, and their cognate recognition sequences, include Factor Xa, thrombin and enterokinase. Typical fusion expression vectors include pGEX (Pharmacia Biotech Inc; Smith, D. B. and Johnson, K. S. (1988) Gene 67:31-40), pMAL (New England Biolabs, Beverly, Mass.) and pRIT5 (Pharmacia, Piscataway, N.J.) which fuse glutathione S-transferase (GST), maltose E binding protein, or protein A, respectively, to the target recombinant protein.

[0411] Purified fusion proteins can be utilized in 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity assays, (e.g., direct assays or competitive assays described in detail below), or to generate antibodies specific for 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins. In a preferred embodiment, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion protein expressed in a retroviral expression vector of the present invention can be utilized to infect bone marrow cells which are subsequently transplanted into irradiated recipients. The pathology of the subject recipient is then examined after sufficient time has passed (e.g., six weeks).

[0412] In another embodiment, a nucleic acid of the invention is expressed in mammalian cells using a mammalian expression vector. Examples of mammalian expression vectors include pCDM8 (Seed, B. (1987) Nature 329:840) and pMT2PC (Kaufman et al. (1987) EMBO J. 6:187-195). When used in mammalian cells, the expression vector's control functions are often provided by viral regulatory elements. For example, commonly used promoters are derived from polyoma, Adenovirus 2, cytomegalovirus and Simian Virus 40. For other suitable expression systems for both prokaryotic and eukaryotic cells see chapters 16 and 17 of Sambrook, J. et al., Molecular Cloning: A Laboratory Manual. 2nd ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989.

[0413] In another embodiment, the recombinant mammalian expression vector is capable of directing expression of the nucleic acid preferentially in a particular cell type (e.g., tissue-specific regulatory elements are used to express the nucleic acid).

[0414] The methods of the invention may further use a recombinant expression vector comprising a DNA molecule of the invention cloned into the expression vector in an antisense orientation. That is, the DNA molecule is operatively linked to a regulatory sequence in a manner which allows for expression (by transcription of the DNA molecule) of an RNA molecule which is antisense to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA. Regulatory sequences operatively linked to a nucleic acid cloned in the antisense orientation can be chosen which direct the continuous expression of the antisense RNA molecule in a variety of cell types, for instance viral promoters and/or enhancers, or regulatory sequences can be chosen which direct constitutive, tissue specific, or cell type specific expression of antisense RNA. The antisense expression vector can be in the form of a recombinant plasmid, phagemid, or attenuated virus in which antisense nucleic acids are produced under the control of a high efficiency regulatory region, the activity of which can be determined by the cell type into which the vector is introduced. For a discussion of the regulation of gene expression using antisense genes, see Weintraub, H. et al., Antisense RNA as a molecular tool for genetic analysis, Reviews—Trends in Genetics, Vol. 1(1) 1986.

[0415] Another aspect of the invention pertains to the use of host cells into which a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecule of the invention is introduced, e.g., a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecule within a recombinant expression vector or a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecule containing sequences which allow it to homologously recombine into a specific site of the host cell's genome. The terms “host cell” and “recombinant host cell” are used interchangeably herein. It is understood that such terms refer not only to the particular subject cell but to the progeny or potential progeny of such a cell. Because certain modifications may occur in succeeding generations due to either mutation or environmental influences, such progeny may not, in fact, be identical to the parent cell, but are still included within the scope of the term as used herein.

[0416] A host cell can be any prokaryotic or eukaryotic cell. For example, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can be expressed in bacterial cells such as E. coli, insect cells, yeast or mammalian cells (such as Chinese hamster ovary cells (CHO) or COS cells). Other suitable host cells are known to those skilled in the art.

[0417] Vector DNA can be introduced into prokaryotic or eukaryotic cells via conventional transformation or transfection techniques. As used herein, the terms “transformation” and “transfection” are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (e.g., DNA) into a host cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran-mediated transfection, lipofection, or electroporation. Suitable methods for transforming or transfecting host cells can be found in Sambrook et al. (Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989), and other laboratory manuals.

[0418] A host cell used in the methods of the invention, such as a prokaryotic or eukaryotic host cell in culture, can be used to produce (i.e., express) a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Accordingly, the invention further provides methods for producing a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein using the host cells of the invention. In one embodiment, the method comprises culturing the host cell of the invention (into which a recombinant expression vector encoding a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein has been introduced) in a suitable medium such that a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein is produced. In another embodiment, the method further comprises isolating a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein from the medium or the host cell.

[0419] Isolated Nucleic Acid Molecules Used in the Methods of the Invention

[0420] The methods of the invention include the use of isolated nucleic acid molecules that encode 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins or biologically active portions thereof, as well as nucleic acid fragments sufficient for use as hybridization probes to identify 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-encoding nucleic acid molecules (e.g., 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA) and fragments for use as PCR primers for the amplification or mutation of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecules. As used herein, the term “nucleic acid molecule” is intended to include DNA molecules (e.g., cDNA or genomic DNA) and RNA molecules (e.g., mRNA) and analogs of the DNA or RNA generated using nucleotide analogs. The nucleic acid molecule can be single-stranded or double-stranded, but preferably is double-stranded DNA.

[0421] A nucleic acid molecule used in the methods of the present invention, e.g., a nucleic acid molecule having the nucleotide sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, or a portion thereof, can be isolated using standard molecular biology techniques and the sequence information provided herein. Using all or portion of the nucleic acid sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125 as a hybridization probe, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecules can be isolated using standard hybridization and cloning techniques (e.g., as described in Sambrook, J., Fritsh, E. F., and Maniatis, T. Molecular Cloning: A Laboratory Manual. 2nd, ed., Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989).

[0422] Moreover, a nucleic acid molecule encompassing all or a portion of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125 can be isolated by the polymerase chain reaction (PCR) using synthetic oligonucleotide primers designed based upon the sequence of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125.

[0423] A nucleic acid used in the methods of the invention can be amplified using cDNA, mRNA or, alternatively, genomic DNA as a template and appropriate oligonucleotide primers according to standard PCR amplification techniques. Furthermore, oligonucleotides corresponding to 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleotide sequences can be prepared by standard synthetic techniques, e.g., using an automated DNA synthesizer.

[0424] In a preferred embodiment, the isolated nucleic acid molecules used in the methods of the invention comprise the nucleotide sequence shown in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, a complement of the nucleotide sequence shown in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, or a portion of any of these nucleotide sequences. A nucleic acid molecule which is complementary to the nucleotide sequence shown in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125 is one which is sufficiently complementary to the nucleotide sequence shown in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, such that it can hybridize to the nucleotide sequence shown in SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, thereby forming a stable duplex.

[0425] In still another preferred embodiment, an isolated nucleic acid molecule used in the methods of the present invention comprises a nucleotide sequence which is at least about 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identical to the entire length of the nucleotide sequence shown in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, or a portion of any of this nucleotide sequence.

[0426] Moreover, the nucleic acid molecules used in the methods of the invention can comprise only a portion of the nucleic acid sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, for example, a fragment which can be used as a probe or primer or a fragment encoding a portion of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, e.g., a biologically active portion of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. The probe/primer typically comprises substantially purified oligonucleotide. The oligonucleotide typically comprises a region of nucleotide sequence that hybridizes under stringent conditions to at least about 12 or 15, preferably about 20 or 25, more preferably about 30, 35, 40, 45, 50, 55, 60, 65, or 75 consecutive nucleotides of a sense sequence of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, of an anti-sense sequence of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, or of a naturally occurring allelic variant or mutant of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125. In one embodiment, a nucleic acid molecule used in the methods of the present invention comprises a nucleotide sequence which is greater than 100, 100-200, 200-300, 300-400, 400-500, 500-600, 600-700, 700-800, 800-900, 900-1000, 1000-1100, 1100-1200, 1200-1300, or more nucleotides in length and hybridizes under stringent hybridization conditions to a nucleic acid molecule of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125.

[0427] As used herein, the term “hybridizes under stringent conditions” is intended to describe conditions for hybridization and washing under which nucleotide sequences that are significantly identical or homologous to each other remain hybridized to each other. Preferably, the conditions are such that sequences at least about 70%, more preferably at least about 80%, even more preferably at least about 85% or 90% identical to each other remain hybridized to each other. Such stringent conditions are known to those skilled in the art and can be found in Current Protocols in Molecular Biology, Ausubel et al., eds., John Wiley & Sons, Inc. (1995), sections 2, 4 and 6. Additional stringent conditions can be found in Molecular Cloning: A Laboratory Manual, Sambrook et al., Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1989), chapters 7, 9 and 11. A preferred, non-limiting example of stringent hybridization conditions includes hybridization in 4× sodium chloride/sodium citrate (SSC), at about 65-70° C. (or hybridization in 4×SSC plus 50% formamide at about 42-50° C.) followed by one or more washes in 1×SSC, at about 65-70° C. A preferred, non-limiting example of highly stringent hybridization conditions includes hybridization in IX SSC, at about 65-70° C. (or hybridization in 1×SSC plus 50% formamide at about 42-50° C.) followed by one or more washes in 0.3×SSC, at about 65-70° C. A preferred, non-limiting example of reduced stringency hybridization conditions includes hybridization in 4×SSC, at about 50-60° C. (or alternatively hybridization in 6×SSC plus 50% formamide at about 40-45° C.) followed by one or more washes in 2×SSC, at about 50-60° C. Ranges intermediate to the above-recited values, e.g., at 65-70° C. or at 42-50° C. are also intended to be encompassed by the present invention. SSPE (1×SSPE is 0. 15M NaCl, 10 mM NaH₂PO₄, and 1.25 mM EDTA, pH 7.4) can be substituted for SSC (1×SSC is 0.15M NaCl and 15 mM sodium citrate) in the hybridization and wash buffers; washes are performed for 15 minutes each after hybridization is complete. The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10° C. less than the melting temperature (T_(m)) of the hybrid, where T_(m) is determined according to the following equations. For hybrids less than 18 base pairs in length, T_(m)(° C.)=2(# of A+T bases)+4(# of G+C bases). For hybrids between 18 and 49 base pairs in length, T_(m)(° C.)=81.5+16.6(log₁₀[Na⁺])+0.41(%G+C)−(600/N), where N is the number of bases in the hybrid, and [Na+] is the concentration of sodium ions in the hybridization buffer ([Na⁺] for 1×SSC=0.165 M). It will also be recognized by the skilled practitioner that additional reagents may be added to hybridization and/or wash buffers to decrease non-specific hybridization of nucleic acid molecules to membranes, for example, nitrocellulose or nylon membranes, including but not limited to blocking agents (e.g., BSA or salmon or herring sperm carrier DNA), detergents (e.g., SDS), chelating agents (e.g., EDTA), Ficoll, PVP and the like. When using nylon membranes, in particular, an additional preferred, non-limiting example of stringent hybridization conditions is hybridization in 0.25-0.5M NaH₂PO₄, 7% SDS at about 65° C., followed by one or more washes at 0.02M NaH₂PO₄, 1% SDS at 65° C., see e.g., Church and Gilbert (1984) Proc. Natl. Acad. Sci. USA 81:1991-1995, (or alternatively 0.2×SSC, 1% SDS).

[0428] In preferred embodiments, the probe further comprises a label group attached thereto, e.g., the label group can be a radioisotope, a fluorescent compound, an enzyme, or an enzyme co-factor. Such probes can be used as a part of a diagnostic test kit for identifying cells or tissue which misexpress a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, such as by measuring a level of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-encoding nucleic acid in a sample of cells from a subject e.g., detecting 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA levels or determining whether a genomic 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene has been mutated or deleted.

[0429] The methods of the invention further encompass the use of nucleic acid molecules that differ from the nucleotide sequence shown in SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, due to degeneracy of the genetic code and thus encode the same 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins as those encoded by the nucleotide sequence shown in SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125. In another embodiment, an isolated nucleic acid molecule included in the methods of the invention has a nucleotide sequence encoding a protein having an amino acid sequence shown in SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126.

[0430] The methods of the invention further include the use of allelic variants of human 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 e.g., functional and non-functional allelic variants. Functional allelic variants are naturally occurring amino acid sequence variants of the human 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein that maintain a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity. Functional allelic variants will typically contain only conservative substitution of one or more amino acids of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126 or substitution, deletion or insertion of non-critical residues in non-critical regions of the protein.

[0431] Non-functional allelic variants are naturally occurring amino acid sequence variants of the human 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein that do not have a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity. Non-functional allelic variants will typically contain a non-conservative substitution, deletion, or insertion or premature truncation of the amino acid sequence of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126, or a substitution, insertion or deletion in critical residues or critical regions of the protein.

[0432] The methods of the present invention may further use non-human orthologues of the human 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Orthologues of the human 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein are proteins that are isolated from non-human organisms and possess the same 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity.

[0433] The methods of the present invention further include the use of nucleic acid molecules comprising the nucleotide sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, or a portion thereof, in which a mutation has been introduced. The mutation may lead to amino acid substitutions at “non-essential” amino acid residues or at “essential” amino acid residues. A “non-essential” amino acid residue is a residue that can be altered from the wild-type sequence of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 (e.g., the sequence of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126) without altering the biological activity, whereas an “essential” amino acid residue is required for biological activity. For example, amino acid residues that are conserved among the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins of the present invention and other members of the family are not likely to be amenable to alteration.

[0434] Mutations can be introduced into SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125 by standard techniques, such as site-directed mutagenesis and PCR-mediated mutagenesis. Preferably, conservative amino acid substitutions are made at one or more predicted non-essential amino acid residues. A “conservative amino acid substitution” is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, a predicted nonessential amino acid residue in a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein is preferably replaced with another amino acid residue from the same side chain family. Alternatively, in another embodiment, mutations can be introduced randomly along all or part of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 coding sequence, such as by saturation mutagenesis, and the resultant mutants can be screened for 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 biological activity to identify mutants that retain activity. Following mutagenesis of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125, the encoded protein can be expressed recombinantly and the activity of the protein can be determined using the assay described herein.

[0435] Another aspect of the invention pertains to the use of isolated nucleic acid molecules which are antisense to the nucleotide sequence of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123 or 125. An “antisense” nucleic acid comprises a nucleotide sequence which is complementary to a “sense” nucleic acid encoding a protein, e.g., complementary to the coding strand of a double-stranded cDNA molecule or complementary to an mRNA sequence. Accordingly, an antisense nucleic acid can hydrogen bond to a sense nucleic acid. The antisense nucleic acid can be complementary to an entire 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 coding strand, or to only a portion thereof. In one embodiment, an antisense nucleic acid molecule is antisense to a “coding region” of the coding strand of a nucleotide sequence encoding a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585. The term “coding region” refers to the region of the nucleotide sequence comprising codons which are translated into amino acid residues. In another embodiment, the antisense nucleic acid molecule is antisense to a “noncoding region” of the coding strand of a nucleotide sequence encoding 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585. The term “noncoding region” refers to 5′ and 3′ sequences which flank the coding region that are not translated into amino acids (also referred to as 5′ and 3′ untranslated regions).

[0436] Given the coding strand sequences encoding 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 disclosed herein, antisense nucleic acids of the invention can be designed according to the rules of Watson and Crick base pairing. The antisense nucleic acid molecule can be complementary to the entire coding region of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA, but more preferably is an oligonucleotide which is antisense to only a portion of the coding or noncoding region of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA. For example, the antisense oligonucleotide can be complementary to the region surrounding the translation start site of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 mRNA. An antisense oligonucleotide can be, for example, about 5, 10, 15, 20, 25, 30, 35, 40, 45 or 50 nucleotides in length. An antisense nucleic acid of the invention can be constructed using chemical synthesis and enzymatic ligation reactions using procedures known in the art. For example, an antisense nucleic acid (e.g., an antisense oligonucleotide) can be chemically synthesized using naturally occurring nucleotides or variously modified nucleotides designed to increase the biological stability of the molecules or to increase the physical stability of the duplex formed between the antisense and sense nucleic acids, e.g., phosphorothioate derivatives and acridine substituted nucleotides can be used. Examples of modified nucleotides which can be used to generate the antisense nucleic acid include 5-fluorouracil, 5-bromouracil, 5-chlorouracil, 5-iodouracil, hypoxanthine, xantine, 4-acetylcytosine, 5-(carboxyhydroxylmethyl) uracil, 5-carboxymethylaminomethyl-2-thiouridine, 5-carboxymethylaminomethyluracil, dihydrouracil, beta-D-galactosylqueosine, inosine, N6-isopentenyladenine, 1-methylguanine, 1-methylinosine, 2,2-dimethylguanine, 2-methyladenine, 2-methylguanine, 3-methylcytosine, 5-methylcytosine, N6-adenine, 7-methylguanine, 5-methylaminomethyluracil, 5-methoxyaminomethyl-2-thiouracil, beta-D-mannosylqueosine, 5′-methoxycarboxymethyluracil, 5-methoxyuracil, 2-methylthio-N6-isopentenyladenine, uracil-5-oxyacetic acid (v), wybutoxosine, pseudouracil, queosine, 2-thiocytosine, 5-methyl-2-thiouracil, 2-thiouracil, 4-thiouracil, 5-methyluracil, uracil-5-oxyacetic acid methylester, uracil-5-oxyacetic acid (v), 5-methyl-2-thiouracil, 3-(3-amino-3-N-2-carboxypropyl) uracil, (acp3)w, and 2,6-diaminopurine. Alternatively, the antisense nucleic acid can be produced biologically using an expression vector into which a nucleic acid has been subcloned in an antisense orientation (i.e., RNA transcribed from the inserted nucleic acid will be of an antisense orientation to a target nucleic acid of interest). Antisense nucleic acid molecules used in the methods of the invention are further described above, in section IV.

[0437] In yet another embodiment, the 139, 258, 1261, 1486, 2398, 2414, 7660, 8587, 10183, 10550, 12680, 17921, 32248, 60489 or 93804 nucleic acid molecules used in the methods of the present invention can be modified at the base moiety, sugar moiety or phosphate backbone to improve, e.g., the stability, hybridization, or solubility of the molecule. For example, the deoxyribose phosphate backbone of the nucleic acid molecules can be modified to generate peptide nucleic acids (see Hyrup B. et al. (1996) Bioorganic & Medicinal Chemistry 4 (1): 5-23). As used herein, the terms “peptide nucleic acids” or “PNAs” refer to nucleic acid mimics, e.g., DNA mimics, in which the deoxyribose phosphate backbone is replaced by a pseudopeptide backbone and only the four natural nucleobases are retained. The neutral backbone of PNAs has been shown to allow for specific hybridization to DNA and RNA under conditions of low ionic strength. The synthesis of PNA oligomers can be performed using standard solid phase peptide synthesis protocols as described in Hyrup B. et al. (1996) supra; Perry-O'eefe et al. (1996) Proc. Natl. Acad. Sci. 93:14670-675.

[0438] PNAs of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecules can be used in the therapeutic and diagnostic applications described herein. For example, PNAs can be used as antisense or antigene agents for sequence-specific modulation of gene expression by, for example, inducing transcription or translation arrest or inhibiting replication. PNAs of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecules can also be used in the analysis of single base pair mutations in a gene, (e.g., by PNA-directed PCR clamping); as ‘artificial restriction enzymes’ when used in combination with other enzymes, (e.g., SI nucleases (Hyrup B. et al. (1996) supra)); or as probes or primers for DNA sequencing or hybridization (Hyrup B. et al. (1996) supra; Perry-O'Keefe et al. (1996) supra).

[0439] In another embodiment, PNAs of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be modified, (e.g., to enhance their stability or cellular uptake), by attaching lipophilic or other helper groups to PNA, by the formation of PNA-DNA chimeras, or by the use of liposomes or other techniques of drug delivery known in the art. For example, PNA-DNA chimeras of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid molecules can be generated which may combine the advantageous properties of PNA and DNA. Such chimeras allow DNA recognition enzymes, (e.g., RNAse H and DNA polymerases), to interact with the DNA portion while the PNA portion would provide high binding affinity and specificity. PNA-DNA chimeras can be linked using linkers of appropriate lengths selected in terms of base stacking, number of bonds between the nucleobases, and orientation (Hyrup B. et al. (1996) supra). The synthesis of PNA-DNA chimeras can be performed as described in Hyrup B. et al. (1996) supra and Finn P. J. et al. (1996) Nucleic Acids Res. 24 (17): 3357-63. For example, a DNA chain can be synthesized on a solid support using standard phosphoramidite coupling chemistry and modified nucleoside analogs, e.g., 5′-(4-methoxytrityl)amino-5′-deoxy-thymidine phosphoramidite, can be used as a between the PNA and the 5′ end of DNA (Mag, M. et al. (1989) Nucleic Acid Res. 17: 5973-88). PNA monomers are then coupled in a stepwise manner to produce a chimeric molecule with a 5′ PNA segment and a 3′ DNA segment (Finn P. J. et al. (1996) supra). Alternatively, chimeric molecules can be synthesized with a 5′ DNA segment and a 3′ PNA segment (Peterser, K. H. et al. (1975) Bioorganic Med. Chem. Lett. 5: 1119-11124).

[0440] In other embodiments, the oligonucleotide used in the methods of the invention may include other appended groups such as peptides (e.g., for targeting host cell receptors in vivo), or agents facilitating transport across the cell membrane (see, e.g., Letsinger et al. (1989) Proc. Natl. Acad. Sci. USA 86:6553-6556; Lemaitre et al. (1987) Proc. Natl. Acad. Sci. USA 84:648-652; PCT Publication No. WO88/09810) or the blood-brain barrier (see, e.g., PCT Publication No. WO89/10134). In addition, oligonucleotides can be modified with hybridization-triggered cleavage agents (See, e.g., Krol et al. (1988) Bio-Techniques 6:958-976) or intercalating agents. (See, e.g., Zon (1988) Pharm. Res. 5:539-549). To this end, the oligonucleotide may be conjugated to another molecule, (e.g., a peptide, hybridization triggered cross-linking agent, transport agent, or hybridization-triggered cleavage agent).

[0441] Isolated 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400. 1452 or 6585 Proteins and Anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 Antibodies Used in the Methods of the Invention

[0442] The methods of the invention include the use of isolated 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins, and biologically active portions thereof, as well as polypeptide fragments suitable for use as immunogens to raise anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibodies. In one embodiment, native 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins can be isolated from cells or tissue sources by an appropriate purification scheme using standard protein purification techniques. In another embodiment, 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins are produced by recombinant DNA techniques. Alternative to recombinant expression, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or polypeptide can be synthesized chemically using standard peptide synthesis techniques.

[0443] As used herein, a “biologically active portion” of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein includes a fragment of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein having a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity. Biologically active portions of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein include peptides comprising amino acid sequences sufficiently identical to or derived from the amino acid sequence of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, e.g., the amino acid sequence shown in SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126 which include fewer amino acids than the full length 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins, and exhibit at least one activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Typically, biologically active portions comprise a domain or motif with at least one activity of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein (e.g., the N-terminal region of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein that is believed to be involved in the regulation of apoptotic activity). A biologically active portion of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can be a polypeptide which is, for example, 25, 50, 75, 100, 125, 150, 175, 200, 250, 300 or more amino acids in length. Biologically active portions of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can be used as targets for developing agents which modulate a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 activity.

[0444] In a preferred embodiment, the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein used in the methods of the invention has an amino acid sequence shown in SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126. In other embodiments, the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein is substantially identical to SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126, and retains the functional activity of the protein of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126, yet differs in amino acid sequence due to natural allelic variation or mutagenesis, as described in detail in subsection V above. Accordingly, in another embodiment, the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein used in the methods of the invention is a protein which comprises an amino acid sequence at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more identical to SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126.

[0445] To determine the percent identity of two amino acid sequences or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-identical sequences can be disregarded for comparison purposes). In a preferred embodiment, the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, even more preferably at least 60%, and even more preferably at least 70%, 80%, or 90% of the length of the reference sequence (e.g., when aligning a second sequence to the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 amino acid sequence of SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126, having 500 amino acid residues, at least 75, preferably at least 150, more preferably at least 225, even more preferably at least 300, and even more preferably at least 400 or more amino acid residues are aligned). The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position (as used herein amino acid or nucleic acid “identity” is equivalent to amino acid or nucleic acid “homology”). The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences.

[0446] The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In a preferred embodiment, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch (J. Mol. Biol. 48:444-453 (1970)) algorithm which has been incorporated into the GAP program in the GCG software package, using either a Blosum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. In yet another preferred embodiment, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package, using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. In another embodiment, the percent identity between two amino acid or nucleotide sequences is determined using the algorithm of E. Meyers and W. Miller (Comput. Appl. Biosci. 4:11-17 (1988)) which has been incorporated into the ALIGN program (version 2.0 or 2.0U), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4.

[0447] The methods of the invention may also use 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 chimeric or fusion proteins. As used herein, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 “chimeric protein” or “fusion protein” comprises a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide operatively linked to a non-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide. An “1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 molecule, whereas a “non-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide” refers to a polypeptide having an amino acid sequence corresponding to a protein which is not substantially homologous to the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, e.g., a protein which is different from the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein and which is derived from the same or a different organism. Within a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion protein the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide can correspond to all or a portion of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. In a preferred embodiment, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion protein comprises at least one biologically active portion of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. In another preferred embodiment, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion protein comprises at least two biologically active portions of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Within the fusion protein, the term “operatively linked” is intended to indicate that the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide and the non-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide are fused in-frame to each other. The non-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide can be fused to the N-terminus or C-terminus of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide.

[0448] For example, in one embodiment, the fusion protein is a GST-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion protein in which the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequences are fused to the C-terminus of the GST sequences. Such fusion proteins can facilitate the purification of recombinant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585.

[0449] In another embodiment, this fusion protein is a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein containing a heterologous signal sequence at its N-terminus. In certain host cells (e.g., mammalian host cells), expression and/or secretion of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be increased through use of a heterologous signal sequence.

[0450] The 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion proteins used in the methods of the invention can be incorporated into pharmaceutical compositions and administered to a subject in vivo. The 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion proteins can be used to affect the bioavailability of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate. Use of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fusion proteins may be useful therapeutically for the treatment of disorders caused by, for example, (i) aberrant modification or mutation of a gene encoding a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein; (ii) mis-regulation of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 gene; and (iii) aberrant post-translational modification of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein.

[0451] Moreover, the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-fusion proteins used in the methods of the invention can be used as immunogens to produce anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibodies in a subject, to purify 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 ligands and in screening assays to identify molecules which inhibit the interaction of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 substrate.

[0452] Preferably, a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 chimeric or fusion protein used in the methods of the invention is produced by standard recombinant DNA techniques. For example, DNA fragments coding for the different polypeptide sequences are ligated together in-frame in accordance with conventional techniques, for example by employing blunt-ended or stagger-ended termini for ligation, restriction enzyme digestion to provide for appropriate termini, filling-in of cohesive ends as appropriate, alkaline phosphatase treatment to avoid undesirable joining, and enzymatic ligation. In another embodiment, the fusion gene can be synthesized by conventional techniques including automated DNA synthesizers. Alternatively, PCR amplification of gene fragments can be carried out using anchor primers which give rise to complementary overhangs between two consecutive gene fragments which can subsequently be annealed and reamplified to generate a chimeric gene sequence (see, for example, Current Protocols in Molecular Biology, eds. Ausubel et al. John Wiley & Sons: 1992). Moreover, many expression vectors are commercially available that already encode a fusion moiety (e.g., a GST polypeptide). A 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-encoding nucleic acid can be cloned into such an expression vector such that the fusion moiety is linked in-frame to the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein.

[0453] The present invention also pertains to the use of variants of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins which function as either 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 agonists (mimetics) or as 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antagonists. Variants of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins can be generated by mutagenesis, e.g., discrete point mutation or truncation of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. An agonist of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins can retain substantially the same, or a subset, of the biological activities of the naturally occurring form of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. An antagonist of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can inhibit one or more of the activities of the naturally occurring form of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein by, for example, competitively modulating a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585-mediated activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Thus, specific biological effects can be elicited by treatment with a variant of limited function. In one embodiment, treatment of a subject with a variant having a subset of the biological activities of the naturally occurring form of the protein has fewer side effects in a subject relative to treatment with the naturally occurring form of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein.

[0454] In one embodiment, variants of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein which function as either 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 agonists (mimetics) or as 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antagonists can be identified by screening combinatorial libraries of mutants, e.g., truncation mutants, of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein for 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein agonist or antagonist activity. In one embodiment, a variegated library of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 variants is generated by combinatorial mutagenesis at the nucleic acid level and is encoded by a variegated gene library. A variegated library of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 variants can be produced by, for example, enzymatically ligating a mixture of synthetic oligonucleotides into gene sequences such that a degenerate set of potential 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequences is expressible as individual polypeptides, or alternatively, as a set of larger fusion proteins (e.g., for phage display) containing the set of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequences therein. There are a variety of methods which can be used to produce libraries of potential 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 variants from a degenerate oligonucleotide sequence. Chemical synthesis of a degenerate gene sequence can be performed in an automatic DNA synthesizer, and the synthetic gene then ligated into an appropriate expression vector. Use of a degenerate set of genes allows for the provision, in one mixture, of all of the sequences encoding the desired set of potential 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 sequences. Methods for synthesizing degenerate oligonucleotides are known in the art (see, e.g., Narang, S. A. (1983) Tetrahedron 39:3; Itakura et al. (1984) Annu. Rev. Biochem. 53:323; Itakura et al. (1984) Science 198:1056; Ike et al. (1983) Nucleic Acid Res. 11:477).

[0455] In addition, libraries of fragments of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein coding sequence can be used to generate a variegated population of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 fragments for screening and subsequent selection of variants of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. In one embodiment, a library of coding sequence fragments can be generated by treating a double stranded PCR fragment of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 coding sequence with a nuclease under conditions wherein nicking occurs only about once per molecule, denaturing the double stranded DNA, renaturing the DNA to form double stranded DNA which can include sense/antisense pairs from different nicked products, removing single stranded portions from reformed duplexes by treatment with S1 nuclease, and ligating the resulting fragment library into an expression vector. By this method, an expression library can be derived which encodes N-terminal, C-terminal and internal fragments of various sizes of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein.

[0456] Several techniques are known in the art for screening gene products of combinatorial libraries made by point mutations or truncation, and for screening cDNA libraries for gene products having a selected property. Such techniques are adaptable for rapid screening of the gene libraries generated by the combinatorial mutagenesis of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 proteins. The most widely used techniques, which are amenable to high through-put analysis, for screening large gene libraries typically include cloning the gene library into replicable expression vectors, transforming appropriate cells with the resulting library of vectors, and expressing the combinatorial genes under conditions in which detection of a desired activity facilitates isolation of the vector encoding the gene whose product was detected. Recursive ensemble mutagenesis (REM), a new technique which enhances the frequency of functional mutants in the libraries, can be used in combination with the screening assays to identify 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 variants (Arkin and Yourvan (1992) Proc. Natl. Acad. Sci. USA 89:7811-7815; Delgrave et al. (1993) Protein Engineering 6(3):327-331).

[0457] The methods of the present invention further include the use of anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibodies. An isolated 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein, or a portion or fragment thereof, can be used as an immunogen to generate antibodies that bind 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 using standard techniques for polyclonal and monoclonal antibody preparation. A full-length 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein can be used or, alternatively, antigenic peptide fragments of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be used as immunogens. The antigenic peptide of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 comprises at least 8 amino acid residues of the amino acid sequence shown in SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124 or 126, and encompasses an epitope of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 such that an antibody raised against the peptide forms a specific immune complex with the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Preferably, the antigenic peptide comprises at least 10 amino acid residues, more preferably at least 15 amino acid residues, even more preferably at least 20 amino acid residues, and most preferably at least 30 amino acid residues.

[0458] Preferred epitopes encompassed by the antigenic peptide are regions of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 that are located on the surface of the protein, e.g., hydrophilic regions, as well as regions with high antigenicity.

[0459] A 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 immunogen is typically used to prepare antibodies by immunizing a suitable subject, (e.g., rabbit, goat, mouse, or other mammal) with the immunogen. An appropriate immunogenic preparation can contain, for example, recombinantly expressed 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein or a chemically synthesized 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide. The preparation can further include an adjuvant, such as Freund's complete or incomplete adjuvant, or similar immunostimulatory agent. Immunization of a suitable subject with an immunogenic 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 preparation induces a polyclonal anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibody response.

[0460] The term “antibody” as used herein refers to immunoglobulin molecules and immunologically active portions of immunoglobulin molecules, i.e., molecules that contain an antigen binding site which specifically binds (immunoreacts with) an antigen, such as a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585. Examples of immunologically active portions of immunoglobulin molecules include F(ab) and F(ab′)₂ fragments which can be generated by treating the antibody with an enzyme such as pepsin. The invention provides polyclonal and monoclonal antibodies that bind 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 molecules. The term “monoclonal antibody” or “monoclonal antibody composition”, as used herein, refers to a population of antibody molecules that contain only one species of an antigen binding site capable of immunoreacting with a particular epitope of 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585. A monoclonal antibody composition thus typically displays a single binding affinity for a particular 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein with which it immunoreacts.

[0461] Polyclonal anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibodies can be prepared as described above by immunizing a suitable subject with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 immunogen. The anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibody titer in the immunized subject can be monitored over time by standard techniques, such as with an enzyme linked immunosorbent assay (ELISA) using immobilized 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 If desired, the antibody molecules directed against 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 can be isolated from the mammal (e.g., from the blood) and further purified by well known techniques, such as protein A chromatography to obtain the IgG fraction. At an appropriate time after immunization, e.g., when the anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibody titers are highest, antibody-producing cells can be obtained from the subject and used to prepare monoclonal antibodies by standard techniques, such as the hybridoma technique originally described by Kohler and Milstein (1975) Nature 256:495-497) (see also, Brown et al. (1981) J. Immunol. 127:539-46; Brown et al. (1980) J. Biol. Chem. 255:4980-83; Yeh et al. (1976) Proc. Natl. Acad. Sci. USA 76:2927-31; and Yeh et al. (1982) Int. J. Cancer 29:269-75), the more recent human B cell hybridoma technique (Kozbor et al. (1983) Immunol Today 4:72), the EBV-hybridoma technique (Cole et al. (1985) Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, Inc., pp. 77-96) or trioma techniques. The technology for producing monoclonal antibody hybridomas is well known (see generally Kenneth, R. H. in Monoclonal Antibodies: A New Dimension In Biological Analyses, Plenum Publishing Corp., New York, N.Y. (1980); Lerner, E. A. (1981) Yale J. Biol. Med. 54:387-402; Gefter, M. L. et al. (1977) Somatic Cell Genet. 3:231-36). Briefly, an immortal cell line (typically a myeloma) is fused to lymphocytes (typically splenocytes) from a mammal immunized with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 immunogen as described above, and the culture supernatants of the resulting hybridoma cells are screened to identify a hybridoma producing a monoclonal antibody that binds 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585.

[0462] Any of the many well known protocols used for fusing lymphocytes and immortalized cell lines can be applied for the purpose of generating an anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 monoclonal antibody (see, e.g., G. Galfre et al. (1977) Nature 266:55052; Gefter et al. (1977) supra; Lerner (1981) supra; and Kenneth (1980) supra). Moreover, the ordinarily skilled worker will appreciate that there are many variations of such methods which also would be useful. Typically, the immortal cell line (e.g., a myeloma cell line) is derived from the same mammalian species as the lymphocytes. For example, murine hybridomas can be made by fusing lymphocytes from a mouse immunized with an immunogenic preparation of the present invention with an immortalized mouse cell line. Preferred immortal cell lines are mouse myeloma cell lines that are sensitive to culture medium containing hypoxanthine, aminopterin and thymidine (“HAT medium”). Any of a number of myeloma cell lines can be used as a fusion partner according to standard techniques, e.g., the P3-NS1/1-Ag4-1, P3-x63-Ag8.653 or Sp2/O-Ag14 myeloma lines. These mycloma lines are available from ATCC. Typically, HAT-sensitive mouse myeloma cells are fused to mouse splenocytes using polyethylene glycol (“PEG”). Hybridoma cells resulting from the fusion are then selected using HAT medium, which kills unfused and unproductively fused myeloma cells (unfused splenocytes die after several days because they are not transformed). Hybridoma cells producing a monoclonal antibody of the invention are detected by screening the hybridoma culture supernatants for antibodies that bind 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585, e.g., using a standard ELISA assay.

[0463] Alternative to preparing monoclonal antibody-secreting hybridomas, a monoclonal anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibody can be identified and isolated by screening a recombinant combinatorial immunoglobulin library (e.g., an antibody phage display library) with 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 to thereby isolate immunoglobulin library members that bind 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585. Kits for generating and screening phage display libraries are commercially available (e.g., the Pharmacia Recombinant Phage Antibody System, Catalog No. 27-9400-01; and the Stratagene SurfZAP™ Phage Display Kit, Catalog No. 240612). Additionally, examples of methods and reagents particularly amenable for use in generating and screening antibody display library can be found in, for example, Ladner et al. U.S. Pat. No. 5,223,409; Kang et al. PCT International Publication No. WO 92/18619; Dower et al. PCT International Publication No. WO 91/17271; Winter et al. PCT International Publication WO 92/20791; Markland et al. PCT International Publication No. WO 92/15679; Breitling et al. PCT International Publication WO 93/01288; McCafferty et al. PCT International Publication No. WO 92/01047; Garrard et al. PCT International Publication No. WO 92/09690; Ladner et al. PCT International Publication No. WO 90/02809; Fuchs et al. (1991) Bio/Technology 9:1370-1372; Hay et al. (1992) Hum. Antibod. Hybridomas 3:81-85; Huse et al. (1989) Science 246:1275-1281; Griffiths et al. (1993) EMBO J 12:725-734; Hawkins et al. (1992) J. Mol. Biol. 226:889-896; Clarkson et al. (1991) Nature 352:624-628; Gram et al. (1992) Proc. Natl. Acad. Sci. USA 89:3576-3580; Garrad et al. (1991) Bio/Technology 9:1373-1377; Hoogenboom et al. (1991) Nuc. Acid Res. 19:4133-4137; Barbas et al. (1991) Proc. Natl. Acad. Sci. USA 88:7978-7982; and McCafferty et al. (1990) Nature 348:552-554.

[0464] Additionally, recombinant anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibodies, such as chimeric and humanized monoclonal antibodies, comprising both human and non-human portions, which can be made using standard recombinant DNA techniques, are within the scope of the methods of the invention. Such chimeric and humanized monoclonal antibodies can be produced by recombinant DNA techniques known in the art, for example using-methods described in Robinson et al. International Application No. PCT/US86/02269; Akira, et al. European Patent Application 184,187; Taniguchi, M., European Patent Application 171,496; Morrison et al. European Patent Application 173,494; Neuberger et al. PCT International Publication No. WO 86/01533; Cabilly et al. U.S. Pat. No. 4,816,567; Cabilly et al. European Patent Application 125,023; Better et al. (1988) Science 240:1041-1043; Liu et al. (1987) Proc. Natl. Acad. Sci. USA 84:3439-3443; Liu et al. (1987) J. Immunol. 139:3521-3526; Sun et al. (1987) Proc. Natl. Acad. Sci. USA 84:214-218; Nishimura et al. (1987) Canc. Res. 47:999-1005; Wood et al. (1985) Nature 314:446-449; Shaw et al. (1988) J. Natl. Cancer Inst. 80:1553-1559; Morrison, S. L. (1985) Science 229:1202-1207; Oi et al. (1986) BioTechniques 4:214; Winter U.S. Pat. No. 5,225,539; Jones et al. (1986) Nature 321:552-525; Verhoeyan et al. (1988) Science 239:1534; and Beidler et al. (1988) J. Immunol. 141:4053-4060.

[0465] An anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibody can be used to detect 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein (e.g., in a cellular lysate or cell supernatant) in order to evaluate the abundance and pattern of expression of the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 protein. Anti-1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 antibodies can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include ¹²⁵I, ¹³¹I, ³⁵S or ³H.

[0466] This invention is further illustrated by the following examples which should not be construed as limiting. The contents of all references, patents and published patent applications cited throughout this application, as well as the Figure and the Sequence Listing is incorporated herein by reference.

EXAMPLES Example 1 Tissue Distribution of Using Taqman™ Analysis

[0467] This example describes the TaqMan™ procedure. The Taqman™ procedure is a quantitative, reverse transcription PCR-based approach for detecting mRNA. The RT-PCR reaction exploits the 5′ nuclease activity of AmpliTaq Gold™ DNA Polymerase to cleave a TaqMan™ probe during PCR. Briefly, cDNA was generated from the samples of interest, e.g., heart, kidney, liver, skeletal muscle, and various vessels, and used as the starting material for PCR amplification. In addition to the 5′ and 3′ gene-specific primers, a gene-specific oligonucleotide probe (complementary to the region being amplified) was included in the reaction (i.e., the Taqman™ probe). The TaqMan™ probe includes the oligonucleotide with a fluorescent reporter dye covalently linked to the 5′ end of the probe (such as FAM (6-carboxyfluorescein), TET (6-carboxy-4,7,2′,7′-tetrachlorofluorescein), JOE (6-carboxy-4,5-dichloro-2,7-dimethoxyfluorescein), or VIC) and a quencher dye (TAMRA (6-carboxy-N,N,N′,N′-tetramethylrhodamine) at the 3′ end of the probe.

[0468] During the PCR reaction, cleavage of the probe separates the reporter dye and the quencher dye, resulting in increased fluorescence of the reporter. Accumulation of PCR products is detected directly by monitoring the increase in fluorescence of the reporter dye. When the probe is intact, the proximity of the reporter dye to the quencher dye results in suppression of the reporter fluorescence. During PCR, if the target of interest is present, the probe specifically anneals between the forward and reverse primer sites. The 5′-3′ nucleolytic activity of the AmpliTaq™ Gold DNA Polymerase cleaves the probe between the reporter and the quencher only if the probe hybridizes to the target. The probe fragments are then displaced from the target, and polymerization of the strand continues. The 3′ end of the probe is blocked to prevent extension of the probe during PCR. This process occurs in every cycle and does not interfere with the exponential accumulation of product. RNA was prepared using the trizol method and treated with DNase to remove contaminating genomic DNA. cDNA was synthesized using standard techniques. Mock cDNA synthesis in the absence of reverse transcriptase resulted in samples with no detectable PCR amplification of the control gene confirms efficient removal of genomic DNA contamination.

[0469] Equivalents

[0470] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

1 126 1 3866 DNA Homo Sapiens 1 ggaattcctt tttttttttt tttgagatgg agtttcactc ttgttggcca ggctggagtg 60 caatggcaca atctcagctt actgcaacct ccgcctcccg ggttcaagcg attctcctgc 120 ctcagcctct caagtagctg ggattacagg catgtgccac cacccctggc taactaattt 180 cttttctatt tagtagagat ggggtttcac catgttggtc aggctggtct tgaactcctg 240 acctcaggtg atccacttgc cttggcctcc caaagtgcta ggattacagc cgtgaaactg 300 tgcctggctg attctttttt tgttgttgga tttttgaaac agggtctccc ttggtcgccc 360 aggctggagt gcagtggtgc gatcttggct cactataacc tccacctcct ggtttcaagt 420 gatcctccca ctttagcctc ctgagtagct gtgattacag gcgtgcacca ccacacccgg 480 ctaatttttg tatttttatt agagacaggg tttcaccatg ttggccaggc tgttctcaaa 540 ctcctggact caagggatcc gcctgcctcc acttcccaaa gtcccgagat tacaggtgtg 600 agtcaccatg cctgacctta taattcttaa gtcatttttt ctggtccatt tcttccttag 660 ggtcctcaca acaaatctgc attaggcggt acaataatcc ttaacttcat gattcacaaa 720 aggaagatga agtgattcat gatttagaaa ggggaagtag taagcccact gcacactcct 780 ggatgatgat cctaaatcca gatacagtaa aaatggggta tgggaaggta gaatacaaaa 840 tttggtttaa attaattatc taaatatcta aaaacatttt tggatacatt gttgatgtga 900 atgtaagact gtacagactt cctagaaaac agtttgggtt ccatcttttc atttccccag 960 tgcagttttc tgtagaaatg gaatccgagg atttaagtgg cagagaattg acaattgatt 1020 ccataatgaa caaagtgaga gacattaaaa ataagtttaa aaatgaagac cttactgatg 1080 aactaagctt gaataaaatt tctgctgata ctacagataa ctcgggaact gttaaccaaa 1140 ttatgatgat ggcaaacaac ccagaggact ggttgagttt gttgctcaaa ctagagaaaa 1200 acagtgttcc gctaagtgat gctcttttaa ataaattgat tggtcgttac agtcaagcaa 1260 ttgaagcgct tcccccagat aaatatggcc aaaatgagag ttttgctaga attcaagtga 1320 gatttgctga attaaaagct attcaagagc cagatgatgc acgtgactac tttcaaatgg 1380 ccagagcaaa ctgcaagaaa tttgcttttg ttcatatatc ttttgcacaa tttgaactgt 1440 cacaaggtaa tgtcaaaaaa agtaaacaac ttcttcaaaa agctgtagaa cgtggagcag 1500 taccactaga aatgctggaa attgccctgc ggaatttaaa cctccaaaaa aagcagctgc 1560 tttcagagga ggaaaagaag aatttatcag catctacggt attaactgcc caagaatcat 1620 tttccggttc acttgggcat ttacagaata ggaacaacag ttgtgattcc agaggacaga 1680 ctactaaagc caggttttta tatggagaga acatgccacc acaagatgca gaaataggtt 1740 accggaattc attgagacaa actaacaaaa ctaaacagtc atgcccattt ggaagagtcc 1800 cagttaacct tctaaatagc ccagattgtg atgtgaagac agatgattca gttgtacctt 1860 gttttatgaa aagacaaacc tctagatcag aatgccgaga tttggttgtg cctggatcta 1920 aaccaagtgg aaatgattcc tgtgaattaa gaaatttaaa gtctgttcaa aatagtcatt 1980 tcaaggaacc tctggtgtca gatgaaaaga gttctgaact tattattact gattcaataa 2040 ccctgaagaa taaaacggaa tcaagtcttc tagctaaatt agaagaaact aaagagtatc 2100 aagaaccaga ggttccagag agtaaccaga aacagtggca agctaagaga aagtcagagt 2160 gtattaacca gaatcctgct gcatcttcaa atcactggca gattccggag ttagcccgaa 2220 aagttaatac agagcagaaa cataccactt ttgagcaacc tgtcttttca gtttcaaaac 2280 agtcaccacc aatatcaaca tctaaatggt ttgacccaaa atctatttgt aagacaccaa 2340 gcagcaatac cttggatgat tacatgagct gttttagaac tccagttgta aagaatgact 2400 ttccacctgc ttgtcagttg tcaacacctt atggccaacc tgcctgtttc cagcagcaac 2460 agcatcaaat acttgccact ccacttcaaa atttacaggt tttagcatct tcttcagcaa 2520 atgaatgcat ttcggttaaa ggaagaattt attccatatt aaagcagata ggaagtggag 2580 gttcaagcaa ggtatttcag gtgttaaatg aaaagaaaca gatatatgct ataaaatatg 2640 tgaacttaga agaagcagat aaccaaactc ttgatagtta ccggaacgaa atagcttatt 2700 tgaataaact acaacaacac agtgataaga tcatccgact ttatgattat gaaatcacgg 2760 accagtacat ctacatggta atggagtgtg gaaatattga tcttaatagt tggcttaaaa 2820 agaaaaaatc cattgatcca tgggaacgca agagttactg gaaaaatatg ttagaggcag 2880 ttcacacaat ccatcaacat ggcattgttc acagtgatct taaaccagct aactttctga 2940 tagttgatgg aatgctaaag ctaattgatt ttgggattgc aaaccaaatg caaccagata 3000 caacaagtgt tgttaaagat tctcaggttg gcacagttaa ttatatgcca ccagaagcaa 3060 tcaaagatat gtcttcctcc agagagaatg ggaaatctaa gtcaaagata agccccaaaa 3120 gtgatgtttg gtccttagga tgtattttgt actatatgac ttacgggaaa acaccatttc 3180 agcagataat taatcagatt tctaaattac atgccataat tgatcctaat catgaaattg 3240 aatttcccga tattccagag aaagatcttc aagatgtgtt aaagtgttgt ttaaaaaggg 3300 acccaaaaca gaggatatcc attcctgagc tcctggctca tccatatgtt caaattcaaa 3360 ctcatccagt taaccaaatg gccaagggaa ccactgaaga aatgaaatat gttctgggcc 3420 aacttgttgg tctgaattct cctaactcca ttttgaaagc tgctaaaact ttatatgaac 3480 actatagtgg tggtgaaagt cataattctt catcctccaa gacttttgaa aaaaaaaggg 3540 gaaaaaaatg atttgcagtt attcgtaatg tcagatagga ggtataaaat atattggact 3600 gttatactct tgaatccctg tggaaatcta catttgaaga caacatcact ctgaagtgtt 3660 atcagcaaaa aaaattcagt gagattatct ttaaaagaaa actgtaaaaa tagcaaccac 3720 ttatggcact gtatatattg tagacttgtt ttctctgttt tatgctcttg tgtaatctac 3780 ttgacatcat tttactcttg gaatagtggg tggatagcaa gtatattcta aaaaactttg 3840 taaataaagt tttgtggcta aaatga 3866 2 841 PRT Homo Sapiens 2 Met Asn Lys Val Arg Asp Ile Lys Asn Lys Phe Lys Asn Glu Asp Leu 1 5 10 15 Thr Asp Glu Leu Ser Leu Asn Lys Ile Ser Ala Asp Thr Thr Asp Asn 20 25 30 Ser Gly Thr Val Asn Gln Ile Met Met Met Ala Asn Asn Pro Glu Asp 35 40 45 Trp Leu Ser Leu Leu Leu Lys Leu Glu Lys Asn Ser Val Pro Leu Ser 50 55 60 Asp Ala Leu Leu Asn Lys Leu Ile Gly Arg Tyr Ser Gln Ala Ile Glu 65 70 75 80 Ala Leu Pro Pro Asp Lys Tyr Gly Gln Asn Glu Ser Phe Ala Arg Ile 85 90 95 Gln Val Arg Phe Ala Glu Leu Lys Ala Ile Gln Glu Pro Asp Asp Ala 100 105 110 Arg Asp Tyr Phe Gln Met Ala Arg Ala Asn Cys Lys Lys Phe Ala Phe 115 120 125 Val His Ile Ser Phe Ala Gln Phe Glu Leu Ser Gln Gly Asn Val Lys 130 135 140 Lys Ser Lys Gln Leu Leu Gln Lys Ala Val Glu Arg Gly Ala Val Pro 145 150 155 160 Leu Glu Met Leu Glu Ile Ala Leu Arg Asn Leu Asn Leu Gln Lys Lys 165 170 175 Gln Leu Leu Ser Glu Glu Glu Lys Lys Asn Leu Ser Ala Ser Thr Val 180 185 190 Leu Thr Ala Gln Glu Ser Phe Ser Gly Ser Leu Gly His Leu Gln Asn 195 200 205 Arg Asn Asn Ser Cys Asp Ser Arg Gly Gln Thr Thr Lys Ala Arg Phe 210 215 220 Leu Tyr Gly Glu Asn Met Pro Pro Gln Asp Ala Glu Ile Gly Tyr Arg 225 230 235 240 Asn Ser Leu Arg Gln Thr Asn Lys Thr Lys Gln Ser Cys Pro Phe Gly 245 250 255 Arg Val Pro Val Asn Leu Leu Asn Ser Pro Asp Cys Asp Val Lys Thr 260 265 270 Asp Asp Ser Val Val Pro Cys Phe Met Lys Arg Gln Thr Ser Arg Ser 275 280 285 Glu Cys Arg Asp Leu Val Val Pro Gly Ser Lys Pro Ser Gly Asn Asp 290 295 300 Ser Cys Glu Leu Arg Asn Leu Lys Ser Val Gln Asn Ser His Phe Lys 305 310 315 320 Glu Pro Leu Val Ser Asp Glu Lys Ser Ser Glu Leu Ile Ile Thr Asp 325 330 335 Ser Ile Thr Leu Lys Asn Lys Thr Glu Ser Ser Leu Leu Ala Lys Leu 340 345 350 Glu Glu Thr Lys Glu Tyr Gln Glu Pro Glu Val Pro Glu Ser Asn Gln 355 360 365 Lys Gln Trp Gln Ala Lys Arg Lys Ser Glu Cys Ile Asn Gln Asn Pro 370 375 380 Ala Ala Ser Ser Asn His Trp Gln Ile Pro Glu Leu Ala Arg Lys Val 385 390 395 400 Asn Thr Glu Gln Lys His Thr Thr Phe Glu Gln Pro Val Phe Ser Val 405 410 415 Ser Lys Gln Ser Pro Pro Ile Ser Thr Ser Lys Trp Phe Asp Pro Lys 420 425 430 Ser Ile Cys Lys Thr Pro Ser Ser Asn Thr Leu Asp Asp Tyr Met Ser 435 440 445 Cys Phe Arg Thr Pro Val Val Lys Asn Asp Phe Pro Pro Ala Cys Gln 450 455 460 Leu Ser Thr Pro Tyr Gly Gln Pro Ala Cys Phe Gln Gln Gln Gln His 465 470 475 480 Gln Ile Leu Ala Thr Pro Leu Gln Asn Leu Gln Val Leu Ala Ser Ser 485 490 495 Ser Ala Asn Glu Cys Ile Ser Val Lys Gly Arg Ile Tyr Ser Ile Leu 500 505 510 Lys Gln Ile Gly Ser Gly Gly Ser Ser Lys Val Phe Gln Val Leu Asn 515 520 525 Glu Lys Lys Gln Ile Tyr Ala Ile Lys Tyr Val Asn Leu Glu Glu Ala 530 535 540 Asp Asn Gln Thr Leu Asp Ser Tyr Arg Asn Glu Ile Ala Tyr Leu Asn 545 550 555 560 Lys Leu Gln Gln His Ser Asp Lys Ile Ile Arg Leu Tyr Asp Tyr Glu 565 570 575 Ile Thr Asp Gln Tyr Ile Tyr Met Val Met Glu Cys Gly Asn Ile Asp 580 585 590 Leu Asn Ser Trp Leu Lys Lys Lys Lys Ser Ile Asp Pro Trp Glu Arg 595 600 605 Lys Ser Tyr Trp Lys Asn Met Leu Glu Ala Val His Thr Ile His Gln 610 615 620 His Gly Ile Val His Ser Asp Leu Lys Pro Ala Asn Phe Leu Ile Val 625 630 635 640 Asp Gly Met Leu Lys Leu Ile Asp Phe Gly Ile Ala Asn Gln Met Gln 645 650 655 Pro Asp Thr Thr Ser Val Val Lys Asp Ser Gln Val Gly Thr Val Asn 660 665 670 Tyr Met Pro Pro Glu Ala Ile Lys Asp Met Ser Ser Ser Arg Glu Asn 675 680 685 Gly Lys Ser Lys Ser Lys Ile Ser Pro Lys Ser Asp Val Trp Ser Leu 690 695 700 Gly Cys Ile Leu Tyr Tyr Met Thr Tyr Gly Lys Thr Pro Phe Gln Gln 705 710 715 720 Ile Ile Asn Gln Ile Ser Lys Leu His Ala Ile Ile Asp Pro Asn His 725 730 735 Glu Ile Glu Phe Pro Asp Ile Pro Glu Lys Asp Leu Gln Asp Val Leu 740 745 750 Lys Cys Cys Leu Lys Arg Asp Pro Lys Gln Arg Ile Ser Ile Pro Glu 755 760 765 Leu Leu Ala His Pro Tyr Val Gln Ile Gln Thr His Pro Val Asn Gln 770 775 780 Met Ala Lys Gly Thr Thr Glu Glu Met Lys Tyr Val Leu Gly Gln Leu 785 790 795 800 Val Gly Leu Asn Ser Pro Asn Ser Ile Leu Lys Ala Ala Lys Thr Leu 805 810 815 Tyr Glu His Tyr Ser Gly Gly Glu Ser His Asn Ser Ser Ser Ser Lys 820 825 830 Thr Phe Glu Lys Lys Arg Gly Lys Lys 835 840 3 1751 DNA Homo Sapiens 3 gcgagatgac tgcagagatt tgaaaaatgg caacaaatga aagtgtcagc atctttagtt 60 cagcatcctt ggctgtggaa tatgtagatt cacttttacc tgagaatcct ctgcaagaac 120 catttaaaaa tgcttggaac tatatgttga ataattatac aaagttccag attgcaacat 180 ggggatccct tatagttcat gaagcccttt atttcttatt ctgtttacct ggatttttat 240 ttcaatttat accttatatg aaaaaataca aaattcaaaa ggataagcca gagacatggg 300 aaaaccaatg gaagtgtttc aaagttcttc tctttaatca cttctgtatc cagctgcctt 360 tgatttgtgg aacctattat tttacagagt atttcaatat tccttatgat tgggaaagaa 420 tgccaagatg gtattttctt ttggcaagat gctttggttg tgcagtcatt gaagatactt 480 ggcactattt tctgcataga ctcttacacc acaaaagaat atacaagtat attcataaag 540 ttcatcatga gtttcaggct ccatttggaa tggaagctga atatgcacat cctttggaga 600 ctctaattct tggaactgga tttttcattg gaatcgtgct tttgtgtgat catgtaattc 660 ttctttgggc atgggtgacc attcgtttat tagaaactat tgatgtccat agtggttatg 720 atattcctct caacccttta aatctgatcc ctttctatgc tggttctcgg catcatgatt 780 tccaccacat gaacttcatt ggaaactatg cttcaacatt tacatggtgg gatcgaattt 840 ttggaacaga ctctcagtat aatgcctata atgaaaagag gaagaagttt gagaaaaaga 900 ctgaataaat atctcacgta aaccttcctg aaagataaac gttttcctga attcagaaac 960 tagtagctaa cattgcttct ggagagcaga aataagcatg tcttctggct actaagtgat 1020 aaaaagaaca ttaacaacct ttaattacct tcctagtggg aactttttct actttaccta 1080 caagttctat atatgtagaa atgaataaat atatatttaa gtacagtttt catgaggaag 1140 ttttaaaaga ccatgttcct aagcttccaa gaaggttttg gatactagaa gtattaatct 1200 atggcttttc tcccagtaaa accataggcc tgaagttcac attgggtctt taaatctttt 1260 agatatatac tggtcatttc agaaaattct tcatagtggt attggcctta tatttaactt 1320 tttttttatt ttttttttga gacaaagcca cactctgtct ccttgtctgg agtgtggtgg 1380 cacagtctca gctcactgca acctctgcct cccagttcaa gcaattcttc tgcctcagcc 1440 tcccaagtag ctgggattac aggcacccgc caccacgccc agctaatttt tgtatttttg 1500 tagagatggg gtttctcgat gttggccagg ctggtctcaa acttctgacc tcaagtgatc 1560 tgcccacctt ggcctcccaa agtgctggga ttacaggtgt aagccactgc gcccggcctt 1620 tttaacttta aacatgtttt agaattcacc taaagatcaa aatatcatgg attgaacctc 1680 atcaattgat agcagtgagt gactgaagct tccaaatcaa gaaaagccgg caccaagaac 1740 ttccattcta a 1751 4 293 PRT Homo Sapiens 4 Met Ala Thr Asn Glu Ser Val Ser Ile Phe Ser Ser Ala Ser Leu Ala 1 5 10 15 Val Glu Tyr Val Asp Ser Leu Leu Pro Glu Asn Pro Leu Gln Glu Pro 20 25 30 Phe Lys Asn Ala Trp Asn Tyr Met Leu Asn Asn Tyr Thr Lys Phe Gln 35 40 45 Ile Ala Thr Trp Gly Ser Leu Ile Val His Glu Ala Leu Tyr Phe Leu 50 55 60 Phe Cys Leu Pro Gly Phe Leu Phe Gln Phe Ile Pro Tyr Met Lys Lys 65 70 75 80 Tyr Lys Ile Gln Lys Asp Lys Pro Glu Thr Trp Glu Asn Gln Trp Lys 85 90 95 Cys Phe Lys Val Leu Leu Phe Asn His Phe Cys Ile Gln Leu Pro Leu 100 105 110 Ile Cys Gly Thr Tyr Tyr Phe Thr Glu Tyr Phe Asn Ile Pro Tyr Asp 115 120 125 Trp Glu Arg Met Pro Arg Trp Tyr Phe Leu Leu Ala Arg Cys Phe Gly 130 135 140 Cys Ala Val Ile Glu Asp Thr Trp His Tyr Phe Leu His Arg Leu Leu 145 150 155 160 His His Lys Arg Ile Tyr Lys Tyr Ile His Lys Val His His Glu Phe 165 170 175 Gln Ala Pro Phe Gly Met Glu Ala Glu Tyr Ala His Pro Leu Glu Thr 180 185 190 Leu Ile Leu Gly Thr Gly Phe Phe Ile Gly Ile Val Leu Leu Cys Asp 195 200 205 His Val Ile Leu Leu Trp Ala Trp Val Thr Ile Arg Leu Leu Glu Thr 210 215 220 Ile Asp Val His Ser Gly Tyr Asp Ile Pro Leu Asn Pro Leu Asn Leu 225 230 235 240 Ile Pro Phe Tyr Ala Gly Ser Arg His His Asp Phe His His Met Asn 245 250 255 Phe Ile Gly Asn Tyr Ala Ser Thr Phe Thr Trp Trp Asp Arg Ile Phe 260 265 270 Gly Thr Asp Ser Gln Tyr Asn Ala Tyr Asn Glu Lys Arg Lys Lys Phe 275 280 285 Glu Lys Lys Thr Glu 290 5 1029 DNA Homo Sapiens 5 atggcagagc atgattacca tgaagactat gggttcagca gtttcaatga cagcagccag 60 gaggagcatc aagacttcct gcagttcagc aaggtctttc tgccctgcat gtacctggtg 120 gtgtttgtct gtggtctggt ggggaactct ctggtgctgg tcatatccat cttctaccat 180 aagttgcaga gcctgacgga tgtgttcctg gtgaacctac ccctggctga cctggtgttt 240 gtctgcactc tgcccttctg ggcctatgca ggcatccatg aatgggtgtt tggccaggtc 300 atgtgcaaga gcctactggg catctacact attaacttct acacgtccat gctcatcctc 360 acctgcatca ctgtggatcg tttcattgta gtggttaagg ccaccaaggc ctacaaccag 420 caagccaaga ggatgacctg gggcaaggtc accagcttgc tcatctgggt gatatccctg 480 ctggtttcct tgccccaaat tatctatggc aatgtcttta atctcgacaa gctcatatgt 540 ggttaccatg acgaggcaat ttccactgtg gttcttgcca cccagatgac actggggttc 600 ttcttgccac tgctcaccat gattgtctgc tattcagtca taatcaaaac actgcttcat 660 gctggaggct tccagaagca cagatctcta aagatcatct tcctggtgat ggctgtgttc 720 ctgctgaccc agatgccctt caacctcatg aagttcatcc gcagcacaca ctgggaatac 780 tatgccatga ccagctttca ctacaccatc atggtgacag aggccatcgc atacctgagg 840 gcctgcctta accctgtgct ctatgccttt gtcagcctga agtttcgaaa gaacttctgg 900 aaacttgtga aggacattgg ttgcctccct taccttgggg tctcacatca atggaaatct 960 tctgaggaca attccaagac tttttctgcc tcccacaatg tggaggccac cagcatgttc 1020 cagttatag 1029 6 342 PRT Homo Sapiens 6 Met Ala Glu His Asp Tyr His Glu Asp Tyr Gly Phe Ser Ser Phe Asn 1 5 10 15 Asp Ser Ser Gln Glu Glu His Gln Asp Phe Leu Gln Phe Ser Lys Val 20 25 30 Phe Leu Pro Cys Met Tyr Leu Val Val Phe Val Cys Gly Leu Val Gly 35 40 45 Asn Ser Leu Val Leu Val Ile Ser Ile Phe Tyr His Lys Leu Gln Ser 50 55 60 Leu Thr Asp Val Phe Leu Val Asn Leu Pro Leu Ala Asp Leu Val Phe 65 70 75 80 Val Cys Thr Leu Pro Phe Trp Ala Tyr Ala Gly Ile His Glu Trp Val 85 90 95 Phe Gly Gln Val Met Cys Lys Ser Leu Leu Gly Ile Tyr Thr Ile Asn 100 105 110 Phe Tyr Thr Ser Met Leu Ile Leu Thr Cys Ile Thr Val Asp Arg Phe 115 120 125 Ile Val Val Val Lys Ala Thr Lys Ala Tyr Asn Gln Gln Ala Lys Arg 130 135 140 Met Thr Trp Gly Lys Val Thr Ser Leu Leu Ile Trp Val Ile Ser Leu 145 150 155 160 Leu Val Ser Leu Pro Gln Ile Ile Tyr Gly Asn Val Phe Asn Leu Asp 165 170 175 Lys Leu Ile Cys Gly Tyr His Asp Glu Ala Ile Ser Thr Val Val Leu 180 185 190 Ala Thr Gln Met Thr Leu Gly Phe Phe Leu Pro Leu Leu Thr Met Ile 195 200 205 Val Cys Tyr Ser Val Ile Ile Lys Thr Leu Leu His Ala Gly Gly Phe 210 215 220 Gln Lys His Arg Ser Leu Lys Ile Ile Phe Leu Val Met Ala Val Phe 225 230 235 240 Leu Leu Thr Gln Met Pro Phe Asn Leu Met Lys Phe Ile Arg Ser Thr 245 250 255 His Trp Glu Tyr Tyr Ala Met Thr Ser Phe His Tyr Thr Ile Met Val 260 265 270 Thr Glu Ala Ile Ala Tyr Leu Arg Ala Cys Leu Asn Pro Val Leu Tyr 275 280 285 Ala Phe Val Ser Leu Lys Phe Arg Lys Asn Phe Trp Lys Leu Val Lys 290 295 300 Asp Ile Gly Cys Leu Pro Tyr Leu Gly Val Ser His Gln Trp Lys Ser 305 310 315 320 Ser Glu Asp Asn Ser Lys Thr Phe Ser Ala Ser His Asn Val Glu Ala 325 330 335 Thr Ser Met Phe Gln Leu 340 7 1750 DNA Homo Sapiens 7 gtggccgccg tcgcccggat cccctgagct gcccgccatc ccacgtgacc gcgccgcccc 60 ccagctccac cgctgagccc gctcgccatg gccctcttcg gggccctctt cctagcgctg 120 ctggcaggcg cacatgcaga gttcccaggc tgcaagatcc gcgtcacctc caaggcgctg 180 gagctggtga agcaggaggg gctgcgcttt ctggagcaag agctggagac tatcaccatt 240 ccggacctgc ggggcaaaga aggccacttc tactacaaca tctctgaggt gaaggtcaca 300 gagctgcaac tgacatcttc cgagctcgat ttccagccac agcaggagct gatgcttcaa 360 atcaccaatg cctccttggg gctgcgcttc cggagacagc tgctctactg gttcttctat 420 gatgggggct acatcaacgc ctcagctgag ggtgtgtcca tccgcactgg tctggagctc 480 tcccgggatc ccgctggacg gatgaaagtg tccaatgtct cctgccaggc ctctgtctcc 540 agaatgcacg cggccttcgg gggaaccttc aagaaggtgt atgattttct ctccacgttc 600 atcacctcag ggatgcgctt cctcctcaac cagcagatct gccctgtcct ctaccacgca 660 gggacggtcc tgctcaactc cctcctggac accgtgcctg tgcgcagttc tgtggacgag 720 cttgttggca ttgactattc cctcatgaag gatcctgtgg cttccaccag caacctggac 780 atggacttcc ggggggcctt cttccccctg actgagagga actggagcct ccccaaccgg 840 gcagtggagc cccagctgca ggaggaagag cggatggtgt atgtggcctt ctctgagttc 900 ttcttcgact ctgccatgga gagctacttc cgggcggggg ccctgcagct gttgctggtg 960 ggggacaagg tgccccacga cctggacatg ctgctgaggg ccacctactt tgggagcatt 1020 gtcctgctga gcccagcagt gattgactcc ccattgaagc tggagctgcg ggtcctggcc 1080 ccaccgcgct gcaccatcaa gccctctggc accaccatct ctgtcactgc tagcgtcacc 1140 attgccctgg tcccaccaga ccagcctgag gtccagctgt ccagcatgac tatggacgcc 1200 cgtctcagcg ccaagatggc tctccggggg aaggccctgc gcacgcagct ggacctgcgc 1260 aggttccgaa tctattccaa ccattctgca ctggagtcgc tggctctgat cccattacag 1320 gcccctctga agaccatgct gcagattggg gtgatgccca tgctcaatga gcggacctgg 1380 cgtggggtgc agatcccact acctgagggc atcaactttg tgcatgaggt ggtgacgaac 1440 catgcgggat tcctcaccat cggggctgat ctccactttg ccaaagggct gcgagaggtg 1500 attgagaaga accggcctgc tgatgtcagg gcgtccactg cccccacacc gtccacagca 1560 gctgtctgag ccctcaatcc ccaagctggc agctgtcatt caggacccca acccctctca 1620 gcccctcttt tcccacattc atagcctgta gtgccccctc taacccccag tgccacagag 1680 aagacgggat ttgaagctgt acccaattta attccataat caatctatca attacagtcc 1740 gtccaccacc 1750 8 493 PRT Homo Sapiens 8 Met Ala Leu Phe Gly Ala Leu Phe Leu Ala Leu Leu Ala Gly Ala His 1 5 10 15 Ala Glu Phe Pro Gly Cys Lys Ile Arg Val Thr Ser Lys Ala Leu Glu 20 25 30 Leu Val Lys Gln Glu Gly Leu Arg Phe Leu Glu Gln Glu Leu Glu Thr 35 40 45 Ile Thr Ile Pro Asp Leu Arg Gly Lys Glu Gly His Phe Tyr Tyr Asn 50 55 60 Ile Ser Glu Val Lys Val Thr Glu Leu Gln Leu Thr Ser Ser Glu Leu 65 70 75 80 Asp Phe Gln Pro Gln Gln Glu Leu Met Leu Gln Ile Thr Asn Ala Ser 85 90 95 Leu Gly Leu Arg Phe Arg Arg Gln Leu Leu Tyr Trp Phe Phe Tyr Asp 100 105 110 Gly Gly Tyr Ile Asn Ala Ser Ala Glu Gly Val Ser Ile Arg Thr Gly 115 120 125 Leu Glu Leu Ser Arg Asp Pro Ala Gly Arg Met Lys Val Ser Asn Val 130 135 140 Ser Cys Gln Ala Ser Val Ser Arg Met His Ala Ala Phe Gly Gly Thr 145 150 155 160 Phe Lys Lys Val Tyr Asp Phe Leu Ser Thr Phe Ile Thr Ser Gly Met 165 170 175 Arg Phe Leu Leu Asn Gln Gln Ile Cys Pro Val Leu Tyr His Ala Gly 180 185 190 Thr Val Leu Leu Asn Ser Leu Leu Asp Thr Val Pro Val Arg Ser Ser 195 200 205 Val Asp Glu Leu Val Gly Ile Asp Tyr Ser Leu Met Lys Asp Pro Val 210 215 220 Ala Ser Thr Ser Asn Leu Asp Met Asp Phe Arg Gly Ala Phe Phe Pro 225 230 235 240 Leu Thr Glu Arg Asn Trp Ser Leu Pro Asn Arg Ala Val Glu Pro Gln 245 250 255 Leu Gln Glu Glu Glu Arg Met Val Tyr Val Ala Phe Ser Glu Phe Phe 260 265 270 Phe Asp Ser Ala Met Glu Ser Tyr Phe Arg Ala Gly Ala Leu Gln Leu 275 280 285 Leu Leu Val Gly Asp Lys Val Pro His Asp Leu Asp Met Leu Leu Arg 290 295 300 Ala Thr Tyr Phe Gly Ser Ile Val Leu Leu Ser Pro Ala Val Ile Asp 305 310 315 320 Ser Pro Leu Lys Leu Glu Leu Arg Val Leu Ala Pro Pro Arg Cys Thr 325 330 335 Ile Lys Pro Ser Gly Thr Thr Ile Ser Val Thr Ala Ser Val Thr Ile 340 345 350 Ala Leu Val Pro Pro Asp Gln Pro Glu Val Gln Leu Ser Ser Met Thr 355 360 365 Met Asp Ala Arg Leu Ser Ala Lys Met Ala Leu Arg Gly Lys Ala Leu 370 375 380 Arg Thr Gln Leu Asp Leu Arg Arg Phe Arg Ile Tyr Ser Asn His Ser 385 390 395 400 Ala Leu Glu Ser Leu Ala Leu Ile Pro Leu Gln Ala Pro Leu Lys Thr 405 410 415 Met Leu Gln Ile Gly Val Met Pro Met Leu Asn Glu Arg Thr Trp Arg 420 425 430 Gly Val Gln Ile Pro Leu Pro Glu Gly Ile Asn Phe Val His Glu Val 435 440 445 Val Thr Asn His Ala Gly Phe Leu Thr Ile Gly Ala Asp Leu His Phe 450 455 460 Ala Lys Gly Leu Arg Glu Val Ile Glu Lys Asn Arg Pro Ala Asp Val 465 470 475 480 Arg Ala Ser Thr Ala Pro Thr Pro Ser Thr Ala Ala Val 485 490 9 1212 DNA Homo Sapiens 9 atggcttgca atggcagtgc ggccaggggg cactttgacc ctgaggactt gaacctgact 60 gacgaggcac tgagactcaa gtacctgggg ccccagcaga cagagctgtt catgcccatc 120 tgtgccacat acctgctgat cttcgtggtg ggcgctgtgg gcaatgggct gacctgtctg 180 gtcatcctgc gccacaaggc catgcgcacg cctaccaact actacctctt cagcctggcc 240 gtgtcggacc tgctggtgct gctggtgggc ctgcccctgg agctctatga gatgtggcac 300 aactacccct tcctgctggg cgttggtggc tgctatttcc gcacgctact gtttgagatg 360 gtctgcctgg cctcagtgct caacgtcact gccctgagcg tggaacgcta tgtggccgtg 420 gtgcacccac tccaggccag gtccatggtg acgcgggccc atgtgcgccg agtgcttggg 480 gccgtctggg gtcttgccat gctctgctcc ctgcccaaca ccagcctgca cggcatccgg 540 cagctgcacg tgccctgccg gggcccagtg ccagactcag ctgtttgcat gctggtccgc 600 ccacgggccc tctacaacat ggtagtgcag accaccgcgc tgctcttctt ctgcctgccc 660 atggccatca tgagcgtgct ctacctgctc attgggctgc gactgcggcg ggagaggctg 720 ctgctcatgc aggaggccaa gggcaggggc tctgcagcag ccaggtccag atacacctgc 780 aggctccagc agcacgatcg gggccggaga caagtgacca agatgctgtt tgtcctggtc 840 gtggtgtttg gcatctgctg ggccccgttc cacgccgacc gcgtcatgtg gagcgtcgtg 900 tcacagtgga cagatggcct gcacctggcc ttccagcacg tgcacgtcat ctccggcatc 960 ttcttctacc tgggctcggc ggccaacccc gtgctctata gcctcatgtc cagccgcttc 1020 cgagagacct tccaggaggc cctgtgcctc ggggcctgct gccatcgcct cagaccccgc 1080 cacagctccc acagcctcag caggatgacc acaggcagca ccctgtgtga tgtgggctcc 1140 ctgggcagct gggtccaccc cctggctggg aacgatggcc cagaggcgca gcaagagacc 1200 gatccatcct ga 1212 10 403 PRT Homo Sapiens 10 Met Ala Cys Asn Gly Ser Ala Ala Arg Gly His Phe Asp Pro Glu Asp 1 5 10 15 Leu Asn Leu Thr Asp Glu Ala Leu Arg Leu Lys Tyr Leu Gly Pro Gln 20 25 30 Gln Thr Glu Leu Phe Met Pro Ile Cys Ala Thr Tyr Leu Leu Ile Phe 35 40 45 Val Val Gly Ala Val Gly Asn Gly Leu Thr Cys Leu Val Ile Leu Arg 50 55 60 His Lys Ala Met Arg Thr Pro Thr Asn Tyr Tyr Leu Phe Ser Leu Ala 65 70 75 80 Val Ser Asp Leu Leu Val Leu Leu Val Gly Leu Pro Leu Glu Leu Tyr 85 90 95 Glu Met Trp His Asn Tyr Pro Phe Leu Leu Gly Val Gly Gly Cys Tyr 100 105 110 Phe Arg Thr Leu Leu Phe Glu Met Val Cys Leu Ala Ser Val Leu Asn 115 120 125 Val Thr Ala Leu Ser Val Glu Arg Tyr Val Ala Val Val His Pro Leu 130 135 140 Gln Ala Arg Ser Met Val Thr Arg Ala His Val Arg Arg Val Leu Gly 145 150 155 160 Ala Val Trp Gly Leu Ala Met Leu Cys Ser Leu Pro Asn Thr Ser Leu 165 170 175 His Gly Ile Arg Gln Leu His Val Pro Cys Arg Gly Pro Val Pro Asp 180 185 190 Ser Ala Val Cys Met Leu Val Arg Pro Arg Ala Leu Tyr Asn Met Val 195 200 205 Val Gln Thr Thr Ala Leu Leu Phe Phe Cys Leu Pro Met Ala Ile Met 210 215 220 Ser Val Leu Tyr Leu Leu Ile Gly Leu Arg Leu Arg Arg Glu Arg Leu 225 230 235 240 Leu Leu Met Gln Glu Ala Lys Gly Arg Gly Ser Ala Ala Ala Arg Ser 245 250 255 Arg Tyr Thr Cys Arg Leu Gln Gln His Asp Arg Gly Arg Arg Gln Val 260 265 270 Thr Lys Met Leu Phe Val Leu Val Val Val Phe Gly Ile Cys Trp Ala 275 280 285 Pro Phe His Ala Asp Arg Val Met Trp Ser Val Val Ser Gln Trp Thr 290 295 300 Asp Gly Leu His Leu Ala Phe Gln His Val His Val Ile Ser Gly Ile 305 310 315 320 Phe Phe Tyr Leu Gly Ser Ala Ala Asn Pro Val Leu Tyr Ser Leu Met 325 330 335 Ser Ser Arg Phe Arg Glu Thr Phe Gln Glu Ala Leu Cys Leu Gly Ala 340 345 350 Cys Cys His Arg Leu Arg Pro Arg His Ser Ser His Ser Leu Ser Arg 355 360 365 Met Thr Thr Gly Ser Thr Leu Cys Asp Val Gly Ser Leu Gly Ser Trp 370 375 380 Val His Pro Leu Ala Gly Asn Asp Gly Pro Glu Ala Gln Gln Glu Thr 385 390 395 400 Asp Pro Ser 11 2370 DNA Homo Sapiens 11 cacgagggag cgctaacgtc tttctgtctc cccgcggtgg tgatgacggt gaaaactgag 60 gctgctaagg gcaccctcac ttactccagg atgaggggca tggtggcaat tctcatcgct 120 ttcatgaagc agaggaggat gggtctgaac gactttattc agaagattgc caataactcc 180 tatgcatgca aacaccctga agttcagtcc atcttgaaga tctcccaacc tcaggagcct 240 gagcttatga atgccaaccc ttctcctcca ccaagtcctt ctcagcaaat caaccttggc 300 ccgtcgtcca atcctcatgc taaaccatct gactttcact tcttgaaagt gatcggaaag 360 ggcagttttg gaaaggttct tctagcaaga cacaaggcag aagaagtgtt ctatgcagtc 420 aaagttttac agaagaaagc aatcctgaaa aagaaagagg agaagcatat tatgtcggag 480 cggaatgttc tgttgaagaa tgtgaagcac cctttcctgg tgggccttca cttctctttc 540 cagactgctg acaaattgta ctttgtccta gactacatta atggtggaga gttgttctac 600 catctccaga gggaacgctg cttcctggaa ccacgggctc gtttctatgc tgctgaaata 660 gccagtgcct tgggctacct gcattcactg aacatcgttt atagagactt aaaaccagag 720 aatattttgc tagattcaca gggacacatt gtccttactg atttcggact ctgcaaggag 780 aacattgaac acaacagcac aacatccacc ttctgtggca cgccggagta tctcgcacct 840 gaggtgcttc ataagcagcc ttatgacagg actgtggact ggtggtgcct gggagctgtc 900 ttgtatgaga tgctgtatgg cctgccgcct ttttatagcc gaaacacagc tgaaatgtac 960 gacaacattc tgaacaagcc tctccagctg aaaccaaata ttacaaattc cgcaagacac 1020 ctcctggagg gcctcctgca gaaggacagg acaaagcggc tcggggccaa ggatgacttc 1080 atggagatta agagtcatgt cttcttctcc ttaattaact gggatgatct cattaataag 1140 aagattactc ccccttttaa cccaaatgtg agtgggccca acgagctacg gcactttgac 1200 cccgagttta ccgaagagcc tgtccccaac tccattggca agtcccctga cagcgtcctc 1260 gtcacagcca gcgtcaagga agctgccgag gctttcctag gcttttccta tgcgcctccc 1320 acggactctt tcctctgaac cctgttaggg cttggtttta aaggatttta tgtgtgtttc 1380 cgaatgtttt agttagcctt ttggtggagc cgccagctga caggacatct tacaagagaa 1440 tttgcacatc tctggaagct tagcaatctt attgcacact gttcgctgga attttttgaa 1500 gagcacattc tcctcagtga gctcatgagg ttttcatttt tattcttcct tccaacgtgg 1560 tgctatctct gaaacgagcg ttagagtgcc gccttagacg gaggcaggag tttcgttaga 1620 aagcggacct gttctaaaaa aggtctcctg cagatctgtc tgggctgtga tgacgaatat 1680 tatgaaatgt gccttttctg aagagattgt gttagctcca aagcttttcc tatcgcagtg 1740 tttcagttct ttattttccc ttgtggatat gctgtgtgaa ccgtcgtgtg agtgtggtat 1800 gcctgatcac agatggattt tgttataagc atcaatgtga cacttgcagg acactacaac 1860 gtgggacatt gtttgtttct tccatatttg gaagataaat ttatgtgtag acttttttgt 1920 aagatacggt taataactaa aatttattga aatggtcttg caatgactcg tattcagatg 1980 cctaaagaaa gcattgctgc tacaaatatt tctattttta gaaagggttt ttatggacca 2040 atgccccagt tgtcagtcag agccgttggt gtttttcatt gtttaaaatg tcacctgtaa 2100 aatgggcatt atttatgttt ttttttttgc attcctgata attgtatgta ttgtataaag 2160 aacgtctgta cattgggtta taacactagt atatttaaac ttacaggctt atttgtaatg 2220 taaaccacca ttttaatgta ctgtaattaa catggttata atacgtacaa tccttccctc 2280 atcccatcac acaacttttt ttgtgtgtga taaactgatt ttggtttgca ataaaacctt 2340 gaaaaataaa aaaaaaaaaa aaaaaaaaaa 2370 12 431 PRT Homo Sapiens 12 Met Thr Val Lys Thr Glu Ala Ala Lys Gly Thr Leu Thr Tyr Ser Arg 1 5 10 15 Met Arg Gly Met Val Ala Ile Leu Ile Ala Phe Met Lys Gln Arg Arg 20 25 30 Met Gly Leu Asn Asp Phe Ile Gln Lys Ile Ala Asn Asn Ser Tyr Ala 35 40 45 Cys Lys His Pro Glu Val Gln Ser Ile Leu Lys Ile Ser Gln Pro Gln 50 55 60 Glu Pro Glu Leu Met Asn Ala Asn Pro Ser Pro Pro Pro Ser Pro Ser 65 70 75 80 Gln Gln Ile Asn Leu Gly Pro Ser Ser Asn Pro His Ala Lys Pro Ser 85 90 95 Asp Phe His Phe Leu Lys Val Ile Gly Lys Gly Ser Phe Gly Lys Val 100 105 110 Leu Leu Ala Arg His Lys Ala Glu Glu Val Phe Tyr Ala Val Lys Val 115 120 125 Leu Gln Lys Lys Ala Ile Leu Lys Lys Lys Glu Glu Lys His Ile Met 130 135 140 Ser Glu Arg Asn Val Leu Leu Lys Asn Val Lys His Pro Phe Leu Val 145 150 155 160 Gly Leu His Phe Ser Phe Gln Thr Ala Asp Lys Leu Tyr Phe Val Leu 165 170 175 Asp Tyr Ile Asn Gly Gly Glu Leu Phe Tyr His Leu Gln Arg Glu Arg 180 185 190 Cys Phe Leu Glu Pro Arg Ala Arg Phe Tyr Ala Ala Glu Ile Ala Ser 195 200 205 Ala Leu Gly Tyr Leu His Ser Leu Asn Ile Val Tyr Arg Asp Leu Lys 210 215 220 Pro Glu Asn Ile Leu Leu Asp Ser Gln Gly His Ile Val Leu Thr Asp 225 230 235 240 Phe Gly Leu Cys Lys Glu Asn Ile Glu His Asn Ser Thr Thr Ser Thr 245 250 255 Phe Cys Gly Thr Pro Glu Tyr Leu Ala Pro Glu Val Leu His Lys Gln 260 265 270 Pro Tyr Asp Arg Thr Val Asp Trp Trp Cys Leu Gly Ala Val Leu Tyr 275 280 285 Glu Met Leu Tyr Gly Leu Pro Pro Phe Tyr Ser Arg Asn Thr Ala Glu 290 295 300 Met Tyr Asp Asn Ile Leu Asn Lys Pro Leu Gln Leu Lys Pro Asn Ile 305 310 315 320 Thr Asn Ser Ala Arg His Leu Leu Glu Gly Leu Leu Gln Lys Asp Arg 325 330 335 Thr Lys Arg Leu Gly Ala Lys Asp Asp Phe Met Glu Ile Lys Ser His 340 345 350 Val Phe Phe Ser Leu Ile Asn Trp Asp Asp Leu Ile Asn Lys Lys Ile 355 360 365 Thr Pro Pro Phe Asn Pro Asn Val Ser Gly Pro Asn Glu Leu Arg His 370 375 380 Phe Asp Pro Glu Phe Thr Glu Glu Pro Val Pro Asn Ser Ile Gly Lys 385 390 395 400 Ser Pro Asp Ser Val Leu Val Thr Ala Ser Val Lys Glu Ala Ala Glu 405 410 415 Ala Phe Leu Gly Phe Ser Tyr Ala Pro Pro Thr Asp Ser Phe Leu 420 425 430 13 2347 DNA Homo Sapiens 13 atgagctgca ggtacggtcc ggaatcccgg gtcgacccac gcgtccggct cctagggagg 60 agctggtacc atgggtgtca ggcaacagtt ggccttgctg ctgctgctgc tgctcctgct 120 ctggggcctg gggcagccag tgtggccagt cgctgtggcc ttgaccctgc gctggctcct 180 gggggatccc acatgttgcg tgctacttgg gctggccatg ttagcacggc cctggctcgg 240 cccctgggtg ccccatgggc tgagcctggc agctgcggcc ctggcactaa ccctcctgcc 300 agcacggctg cccccaggac tacgctggct gccggctgat gtgatcttct tggccaagat 360 cctccacctg ggcctgaaga tcaggggatg cttgagccgg cagccgcctg acacctttgt 420 agatgccttc gagcggcgag cacgagcgca gcctggcagg gcactcttgg tgtggacggg 480 gcctggggcc ggctcagtca cctttggtga gctggatgcc cgggcctgcc aggcggcatg 540 ggccctgaag gctgagctgg gtgaccctgc gagcctgtgt gccggggagc ctactgccct 600 ccttgtgctg gcttcccagg ccgttccagc cctgtgtatg tggctggggc tggccaagct 660 gggctgccca acagcctgga tcaacccgca tggccggggg atgcccctgg cgcactctgt 720 gctgagctct ggggcccggg tgctggtggt ggacccagac ctccgggaga gcctggagga 780 gatccttccc aagctgcagg ctgagaacat ccgctgcttc tacctcagcc atacctcccc 840 tacaccaggg gtgggggctc tgggggctgc cctggatgca gcgccctccc acccagtgcc 900 tgctgacctg cgtgctggga tcacatggag aagccctgcc ctcttcatct atacctcggg 960 gaccactggc ctcccgaagc cagccatcct cacgcatgag cgggtactgc agatgagcaa 1020 gatgctgtcc ttatctgggg ccacagctga tgatgtggtt tacacggtcc tgcctctgta 1080 ccacgtgatg ggacttgtcg ttgggatcct cggctgctta gatctcggag ccacctgtgt 1140 tctggccccc aagttctcta cttcctgctt ctgggatgac tgtcggcagc atggcgtgac 1200 agtgatcctg tatgtgggcg agctcctgcg gtacttgtgt aacattcccc agcaaccaga 1260 ggaccggaca catacagtcc gcctggcaat gggcaatgga ctacgggctg atgtgtggga 1320 gaccttccag cagcgcttcg gtcctattcg gatctgggaa gtctacggct ccacagaagg 1380 caacatgggc ttagtcaact atgtggggcg ctgcggggcc ctgggcaaga tgagctgcct 1440 cctccgaatg ctgtccccct ttgagctggt gcagttcgac atggaggcgg cggagcctgt 1500 gagggacaat cagggcttct gcatccctgt agggctaggg gagccggggc tgctgctgac 1560 caaggtggta agccagcaac ccttcgtggg ctaccgcggc ccccgagagc tgtcggaacg 1620 gaagctggtg cgcaacgtgc ggcaatcggg cgacgtttac tacaacaccg gggacgtact 1680 ggccatggac cgcgaaggct tcctctactt ccgcgaccgc ctcggggaca ccttccgatg 1740 gaagggcgag aacgtgtcca cgcacgaggt ggagggcgtg ttgtcgcagg tggacttctt 1800 gcaacaggtt aacgtgtatg gcgtgtgcgt gccaggttgt gagggtaagg tgggcatggc 1860 tgctgtgcag ctagcccccg gccagacttt cgacggggag aagttgtacc agcacgttcg 1920 cgcttggctc cctgcctacg ctacccccca tttcatccgc atccaggacg ccatggaggt 1980 caccagcacg ttcaaactga tgaagacccg gttggtgcgt gagggcttca atgtggggat 2040 cgtggttgac cctctgtttg tactggacaa ccgggcccag tccttccggc ccctgacggc 2100 agaaatgtac caggctgtgt gtgagggaac ctggaggctc tgatcacctg gccaacccac 2160 tggggtaggg gtagggatca aagccagcca cccccacccc aacacactcg gtgtcccttt 2220 catcctgggc ctgtgtgaat cccagcctgg ccataccctc aacctcagtg ggctggaaat 2280 gacagtgggc cctgtagcag tggcagaata aactcagatg tgttcaaaaa aaaaaaaaaa 2340 aaaaaaa 2347 14 690 PRT Homo Sapiens 14 Met Gly Val Arg Gln Gln Leu Ala Leu Leu Leu Leu Leu Leu Leu Leu 1 5 10 15 Leu Trp Gly Leu Gly Gln Pro Val Trp Pro Val Ala Val Ala Leu Thr 20 25 30 Leu Arg Trp Leu Leu Gly Asp Pro Thr Cys Cys Val Leu Leu Gly Leu 35 40 45 Ala Met Leu Ala Arg Pro Trp Leu Gly Pro Trp Val Pro His Gly Leu 50 55 60 Ser Leu Ala Ala Ala Ala Leu Ala Leu Thr Leu Leu Pro Ala Arg Leu 65 70 75 80 Pro Pro Gly Leu Arg Trp Leu Pro Ala Asp Val Ile Phe Leu Ala Lys 85 90 95 Ile Leu His Leu Gly Leu Lys Ile Arg Gly Cys Leu Ser Arg Gln Pro 100 105 110 Pro Asp Thr Phe Val Asp Ala Phe Glu Arg Arg Ala Arg Ala Gln Pro 115 120 125 Gly Arg Ala Leu Leu Val Trp Thr Gly Pro Gly Ala Gly Ser Val Thr 130 135 140 Phe Gly Glu Leu Asp Ala Arg Ala Cys Gln Ala Ala Trp Ala Leu Lys 145 150 155 160 Ala Glu Leu Gly Asp Pro Ala Ser Leu Cys Ala Gly Glu Pro Thr Ala 165 170 175 Leu Leu Val Leu Ala Ser Gln Ala Val Pro Ala Leu Cys Met Trp Leu 180 185 190 Gly Leu Ala Lys Leu Gly Cys Pro Thr Ala Trp Ile Asn Pro His Gly 195 200 205 Arg Gly Met Pro Leu Ala His Ser Val Leu Ser Ser Gly Ala Arg Val 210 215 220 Leu Val Val Asp Pro Asp Leu Arg Glu Ser Leu Glu Glu Ile Leu Pro 225 230 235 240 Lys Leu Gln Ala Glu Asn Ile Arg Cys Phe Tyr Leu Ser His Thr Ser 245 250 255 Pro Thr Pro Gly Val Gly Ala Leu Gly Ala Ala Leu Asp Ala Ala Pro 260 265 270 Ser His Pro Val Pro Ala Asp Leu Arg Ala Gly Ile Thr Trp Arg Ser 275 280 285 Pro Ala Leu Phe Ile Tyr Thr Ser Gly Thr Thr Gly Leu Pro Lys Pro 290 295 300 Ala Ile Leu Thr His Glu Arg Val Leu Gln Met Ser Lys Met Leu Ser 305 310 315 320 Leu Ser Gly Ala Thr Ala Asp Asp Val Val Tyr Thr Val Leu Pro Leu 325 330 335 Tyr His Val Met Gly Leu Val Val Gly Ile Leu Gly Cys Leu Asp Leu 340 345 350 Gly Ala Thr Cys Val Leu Ala Pro Lys Phe Ser Thr Ser Cys Phe Trp 355 360 365 Asp Asp Cys Arg Gln His Gly Val Thr Val Ile Leu Tyr Val Gly Glu 370 375 380 Leu Leu Arg Tyr Leu Cys Asn Ile Pro Gln Gln Pro Glu Asp Arg Thr 385 390 395 400 His Thr Val Arg Leu Ala Met Gly Asn Gly Leu Arg Ala Asp Val Trp 405 410 415 Glu Thr Phe Gln Gln Arg Phe Gly Pro Ile Arg Ile Trp Glu Val Tyr 420 425 430 Gly Ser Thr Glu Gly Asn Met Gly Leu Val Asn Tyr Val Gly Arg Cys 435 440 445 Gly Ala Leu Gly Lys Met Ser Cys Leu Leu Arg Met Leu Ser Pro Phe 450 455 460 Glu Leu Val Gln Phe Asp Met Glu Ala Ala Glu Pro Val Arg Asp Asn 465 470 475 480 Gln Gly Phe Cys Ile Pro Val Gly Leu Gly Glu Pro Gly Leu Leu Leu 485 490 495 Thr Lys Val Val Ser Gln Gln Pro Phe Val Gly Tyr Arg Gly Pro Arg 500 505 510 Glu Leu Ser Glu Arg Lys Leu Val Arg Asn Val Arg Gln Ser Gly Asp 515 520 525 Val Tyr Tyr Asn Thr Gly Asp Val Leu Ala Met Asp Arg Glu Gly Phe 530 535 540 Leu Tyr Phe Arg Asp Arg Leu Gly Asp Thr Phe Arg Trp Lys Gly Glu 545 550 555 560 Asn Val Ser Thr His Glu Val Glu Gly Val Leu Ser Gln Val Asp Phe 565 570 575 Leu Gln Gln Val Asn Val Tyr Gly Val Cys Val Pro Gly Cys Glu Gly 580 585 590 Lys Val Gly Met Ala Ala Val Gln Leu Ala Pro Gly Gln Thr Phe Asp 595 600 605 Gly Glu Lys Leu Tyr Gln His Val Arg Ala Trp Leu Pro Ala Tyr Ala 610 615 620 Thr Pro His Phe Ile Arg Ile Gln Asp Ala Met Glu Val Thr Ser Thr 625 630 635 640 Phe Lys Leu Met Lys Thr Arg Leu Val Arg Glu Gly Phe Asn Val Gly 645 650 655 Ile Val Val Asp Pro Leu Phe Val Leu Asp Asn Arg Ala Gln Ser Phe 660 665 670 Arg Pro Leu Thr Ala Glu Met Tyr Gln Ala Val Cys Glu Gly Thr Trp 675 680 685 Arg Leu 690 15 1157 DNA Homo Sapiens 15 tcccaggtgc ccgtctgatg gggagatggc tgatgcccag aacatttcac tggacagccc 60 agggagtgtg ggggccgtgg cagtgcctgt ggtctttgcc ctaatcttcc tgctgggcac 120 agtgggcaat gggctggtgc tggcagtgct cctgcagcct ggcccgagtg cctggcagga 180 gcctggcagc accacggacc tgttcatcct caacctggcg gtggctgacc tctgcttcat 240 cctgtgctgc gtgcccttcc aggccaccat ctacacgctg gatgcctggc tctttggggc 300 cctcgtctgc aaggccgtgc acctgctcat ctacctcacc atgtacgcca gcagctttac 360 gctggctgct gtctccgtgg acaggtacct ggccgtgcgg cacccgctgc gctcgcgcgc 420 cctgcgcacg ccgcgtaacg cccgcgccgc agtggggctg gtgtggctgc tggcggcgct 480 cttctcggcg ccctacctca gctactacgg caccgtgcgc tacggcgcgc tggagctctg 540 cgtgcccgcc tgggaggacg cgcgccgccg cgccctggac gtggccacct tcgctgccgg 600 ctacctgctg cccgtggctg tggtgagcct ggcctacggg cgcacgctgc gcttcctgtg 660 ggccgccgtg ggtcccgcgg gcgcggcggc ggccgaggcg cggcggaggg cgacgggccg 720 cgcggggcgc gccatgctgg cggtggccgc gctctacgcg ctctgctggg gtccgcacca 780 cgcgctcatc ctgtgcttct ggtacggccg cttcgccttc agcccggcca cctacgcctg 840 ccgcctggcc tcacactgcc tggcctacgc caactcctgc ctcaacccgc tcgtctacgc 900 gctcgcctcg cgccacttcc gcgcgcgctt ccgccgcctg tggccgtgcg gccgccgacg 960 ccgccaccgt gcccgccgcg ccttgcgtcg cgtccgcccc gcgtcctcgg gcccacccgg 1020 ctgccccgga gacgcccggc ctagcgggag gctgctggct ggtggcggcc agggcccgga 1080 gcccagggag ggacccgtcc acggcggaga ggctgcccga ggaccggaat aaaccctgcc 1140 gcctggactc cgcctgt 1157 16 368 PRT Homo Sapiens 16 Met Ala Asp Ala Gln Asn Ile Ser Leu Asp Ser Pro Gly Ser Val Gly 1 5 10 15 Ala Val Ala Val Pro Val Val Phe Ala Leu Ile Phe Leu Leu Gly Thr 20 25 30 Val Gly Asn Gly Leu Val Leu Ala Val Leu Leu Gln Pro Gly Pro Ser 35 40 45 Ala Trp Gln Glu Pro Gly Ser Thr Thr Asp Leu Phe Ile Leu Asn Leu 50 55 60 Ala Val Ala Asp Leu Cys Phe Ile Leu Cys Cys Val Pro Phe Gln Ala 65 70 75 80 Thr Ile Tyr Thr Leu Asp Ala Trp Leu Phe Gly Ala Leu Val Cys Lys 85 90 95 Ala Val His Leu Leu Ile Tyr Leu Thr Met Tyr Ala Ser Ser Phe Thr 100 105 110 Leu Ala Ala Val Ser Val Asp Arg Tyr Leu Ala Val Arg His Pro Leu 115 120 125 Arg Ser Arg Ala Leu Arg Thr Pro Arg Asn Ala Arg Ala Ala Val Gly 130 135 140 Leu Val Trp Leu Leu Ala Ala Leu Phe Ser Ala Pro Tyr Leu Ser Tyr 145 150 155 160 Tyr Gly Thr Val Arg Tyr Gly Ala Leu Glu Leu Cys Val Pro Ala Trp 165 170 175 Glu Asp Ala Arg Arg Arg Ala Leu Asp Val Ala Thr Phe Ala Ala Gly 180 185 190 Tyr Leu Leu Pro Val Ala Val Val Ser Leu Ala Tyr Gly Arg Thr Leu 195 200 205 Arg Phe Leu Trp Ala Ala Val Gly Pro Ala Gly Ala Ala Ala Ala Glu 210 215 220 Ala Arg Arg Arg Ala Thr Gly Arg Ala Gly Arg Ala Met Leu Ala Val 225 230 235 240 Ala Ala Leu Tyr Ala Leu Cys Trp Gly Pro His His Ala Leu Ile Leu 245 250 255 Cys Phe Trp Tyr Gly Arg Phe Ala Phe Ser Pro Ala Thr Tyr Ala Cys 260 265 270 Arg Leu Ala Ser His Cys Leu Ala Tyr Ala Asn Ser Cys Leu Asn Pro 275 280 285 Leu Val Tyr Ala Leu Ala Ser Arg His Phe Arg Ala Arg Phe Arg Arg 290 295 300 Leu Trp Pro Cys Gly Arg Arg Arg Arg His Arg Ala Arg Arg Ala Leu 305 310 315 320 Arg Arg Val Arg Pro Ala Ser Ser Gly Pro Pro Gly Cys Pro Gly Asp 325 330 335 Ala Arg Pro Ser Gly Arg Leu Leu Ala Gly Gly Gly Gln Gly Pro Glu 340 345 350 Pro Arg Glu Gly Pro Val His Gly Gly Glu Ala Ala Arg Gly Pro Glu 355 360 365 17 3763 DNA Homo Sapiens 17 ccgccgcccg ccgaggccgc cgcccggccg cccgaggatg cggccgtccg gcgacgtgga 60 ccgcgcgcgt cgccgccgcc gccgccgccg ccggagggac cttctgctga gccagctctg 120 cttcctggcc tcggtggcgc tgctgctctg gtcgctgtcg agcctgcgag agcagaagga 180 gcttgacctc atggacctcg taggggaaga cagaaagtgg atgatggcga ggaagctgat 240 gcaggtgaac gacactctga cttccgaaga tgccggactc cggaacagca agaactgcac 300 cgaaccagcc ctgcatgaat tccccaatga catcttcaca aacgaggata gaagacaagg 360 tgcggtggtc ctccatgtgc tctgtgccat atacatgttc tatgcgctgg ccattgtgtg 420 tgatgacttc ttcgtccctt ccttggaaaa gatctgtgag cgcctgcacc tcagtgaaga 480 tgtggctggg gccacattca tggcagcggg aagttcagcc ccagagctgt tcacatcggt 540 cataggggtc ttcatcacca aaggcgatgt gggagttggc accatcgtgg gctcagcggt 600 attcaacatc ctgtgcatca ttggtgtctg tgggctcttt gctgggcagg ttgtggctct 660 ttcctcctgg tgcctgctga gggattctat ttactacacg ctgtctgtga tcgcgctcat 720 cgtgtttatt tatgatgaaa aagtttcctg gtgggagtct ttagtccttg tgctgatgta 780 tcttatctac attgtcatca tgaaatataa cgcttgcata catcagtgct ttgagaggag 840 gacaaaaggt gccgggaaca tggtcaacgg attggccaac aatgctgaaa ttgatgacag 900 cagcaactgc gacgcaactg tggtgctact taagaaagca aatttccacc gcaaagcatc 960 agtgatcatg gtagacgagc tgctgtcagc ctacccacac cagctttcct tctctgaggc 1020 tggccttcga atcatgataa ccagccactt tccccccaag acccggctct ccatggccag 1080 tcgcatgttg atcaatgaga gacaaagatt gataaacagc agggcttata ccaacgggga 1140 atctgaggtg gccatcaaaa tcccaattaa gcacaccgtg gagaatggga cagggcccag 1200 cagtgcccca gacaggggcg tgaatgggac acggagggac gatgttgtgg ctgaggctgg 1260 caacgaaaca gagaatgaaa atgaggacaa tgagaatgat gaggaggaag aggaggacga 1320 ggatgatgat gaaggaccgt acacaccatt cgacaccccc tcgggtaaac tggaaacagt 1380 gaaatgggcg ttcacctggc cgctgagttt cgtcttatac ttcactgtac ccaactgcaa 1440 caagccgcgc tgggagaaat ggttcatggt gacgtttgct tcctccacgc tgtggatcgc 1500 agccttctcc tacatgatgg tgtggatggt cacaatcatt ggttacaccc tggggattcc 1560 tgacgtcatc atggggatca ccttcctggc tgctgggacc agcgtgcctg actgcatggc 1620 cagcctcatt gtggccagac aagggatggg ggacatggct gtgtccaact ccattgggag 1680 caacgtgttt gacatcctga ttggcctcgg tctcccctgg gctctgcaga ccctggctgt 1740 ggattacgga tcctacatcc ggctgaatag cagggggctg atctactccg taggcttgct 1800 cctggcctct gtttttgtca cggtgttcgg cgtccacctg aacaagtggc agctggacaa 1860 gaagctgggc tgtgggtgcc tcctcctgta tggtgtgttc ctgtgcttct ccatcatgac 1920 tgagttcaac gtgttcacct ttgtgaacct gcccatgtgc ggggaccact gagccgccgg 1980 gtgcccacag aggctcagct ccttcttttc tgtgcaatac gagacccggc cgcaccccga 2040 gtcacacagg cccccggggc cacggcgttc gtctctcctg tgctgtcctc aggcctccgc 2100 tcctgttttg gtggcccagg ctctcccctg ccccatcctc gctcccccac ctccttgggt 2160 catgcccacc caccctttcc tgcctcctcc gtgtgaagac atccaacatc cacgtgactt 2220 ttccagctcc atttttaaac agtgactgag attctagaaa aactggctgc taactggcct 2280 gagccaggca acactgattc caatccctcc tcctttttta agttatttga tggaagactc 2340 acctaatttg tgacctgaaa ctgttgaaga aatagagagg agggggcccg ttgattacag 2400 agagcatttg ggattttgtt tggtttggag atgatgccta ggttactggg tttgggggga 2460 ttgttttctt ttgggggcct tcccctttta ctccttttct tccagagatc aagagcttct 2520 cttgcatctt cttccactgg gctctggatt aatcaattac ccaaaggctg cacctgccgt 2580 gttgtctggg cttgcatccc agatgtgttg gagtatgcat ggatgtagtg ctttttagag 2640 gagccactgg gcaaggccac caagaacaaa tgcatgacat tttatagcca aggacgcctc 2700 gctaaagtct tatgggcgtc ccctggggtt gggggggcac aaggttttgg aggaagaaga 2760 caacttccct cattccatca tcaccatctc tttctcacta ggttctttct agttttcaag 2820 caatagttct agcctgcctt ggacaagggg gccccagtta aacaaactac ccatccatga 2880 ggtgccaggc agtcaaaaac agaagcttcc ccgacttgtg agtccctgag atgtgctctt 2940 gttgtttggc atttggggtg acagggagtg acccagaggc caccactgct tttcatgcag 3000 gagttacaga cactggtttc ttggaaaatg gagagaagcg cactttgcac agacgtcgtc 3060 aattaagtcc caatttgcca cttggtattg agtacactgg accctgacca ctggctcttg 3120 ggcaaacgtc cttcctcacg gggcgcctcc gccaagccgg cccagctgca cccctccctt 3180 cctggaggga tggccaggga aggagaaaac agagaactga cacctttgaa accacagaat 3240 gtgttacatg cagactcgct caagggcata agttattgtg aacgtttttg ccaatcactg 3300 ctcaacagcc ctgctagatt ttgtatgatg ctgaattatt atgcagacta attccaccca 3360 gttgagacac accatgcttg ttcacttgta tttattgaaa ctgtggattc ttgcccgtgc 3420 tgtcccttgt atttacttta agcactgatc acttatcatt cattcggtat ggttttccct 3480 gtcccttgta cacattctgg tatgaatttg taaaaataac ctgctacaaa ttggttgaat 3540 gtttctgtct gtggtgcgaa ccagcattaa cggatggggc acgtgcccaa ctgaggaaca 3600 ggagaagaaa tcaccaattt gggctctcag agctaagaca cacttattga ttctgttgca 3660 cattttgcac tggtttatgg cgattgtttt cttggacgga tagtgtaaaa taaacttctc 3720 tgttctctat ccaaaaaaaa aaagagtgca ttactttctc ccc 3763 18 644 PRT Homo Sapiens 18 Met Arg Pro Ser Gly Asp Val Asp Arg Ala Arg Arg Arg Arg Arg Arg 1 5 10 15 Arg Arg Arg Arg Asp Leu Leu Leu Ser Gln Leu Cys Phe Leu Ala Ser 20 25 30 Val Ala Leu Leu Leu Trp Ser Leu Ser Ser Leu Arg Glu Gln Lys Glu 35 40 45 Leu Asp Leu Met Asp Leu Val Gly Glu Asp Arg Lys Trp Met Met Ala 50 55 60 Arg Lys Leu Met Gln Val Asn Asp Thr Leu Thr Ser Glu Asp Ala Gly 65 70 75 80 Leu Arg Asn Ser Lys Asn Cys Thr Glu Pro Ala Leu His Glu Phe Pro 85 90 95 Asn Asp Ile Phe Thr Asn Glu Asp Arg Arg Gln Gly Ala Val Val Leu 100 105 110 His Val Leu Cys Ala Ile Tyr Met Phe Tyr Ala Leu Ala Ile Val Cys 115 120 125 Asp Asp Phe Phe Val Pro Ser Leu Glu Lys Ile Cys Glu Arg Leu His 130 135 140 Leu Ser Glu Asp Val Ala Gly Ala Thr Phe Met Ala Ala Gly Ser Ser 145 150 155 160 Ala Pro Glu Leu Phe Thr Ser Val Ile Gly Val Phe Ile Thr Lys Gly 165 170 175 Asp Val Gly Val Gly Thr Ile Val Gly Ser Ala Val Phe Asn Ile Leu 180 185 190 Cys Ile Ile Gly Val Cys Gly Leu Phe Ala Gly Gln Val Val Ala Leu 195 200 205 Ser Ser Trp Cys Leu Leu Arg Asp Ser Ile Tyr Tyr Thr Leu Ser Val 210 215 220 Ile Ala Leu Ile Val Phe Ile Tyr Asp Glu Lys Val Ser Trp Trp Glu 225 230 235 240 Ser Leu Val Leu Val Leu Met Tyr Leu Ile Tyr Ile Val Ile Met Lys 245 250 255 Tyr Asn Ala Cys Ile His Gln Cys Phe Glu Arg Arg Thr Lys Gly Ala 260 265 270 Gly Asn Met Val Asn Gly Leu Ala Asn Asn Ala Glu Ile Asp Asp Ser 275 280 285 Ser Asn Cys Asp Ala Thr Val Val Leu Leu Lys Lys Ala Asn Phe His 290 295 300 Arg Lys Ala Ser Val Ile Met Val Asp Glu Leu Leu Ser Ala Tyr Pro 305 310 315 320 His Gln Leu Ser Phe Ser Glu Ala Gly Leu Arg Ile Met Ile Thr Ser 325 330 335 His Phe Pro Pro Lys Thr Arg Leu Ser Met Ala Ser Arg Met Leu Ile 340 345 350 Asn Glu Arg Gln Arg Leu Ile Asn Ser Arg Ala Tyr Thr Asn Gly Glu 355 360 365 Ser Glu Val Ala Ile Lys Ile Pro Ile Lys His Thr Val Glu Asn Gly 370 375 380 Thr Gly Pro Ser Ser Ala Pro Asp Arg Gly Val Asn Gly Thr Arg Arg 385 390 395 400 Asp Asp Val Val Ala Glu Ala Gly Asn Glu Thr Glu Asn Glu Asn Glu 405 410 415 Asp Asn Glu Asn Asp Glu Glu Glu Glu Glu Asp Glu Asp Asp Asp Glu 420 425 430 Gly Pro Tyr Thr Pro Phe Asp Thr Pro Ser Gly Lys Leu Glu Thr Val 435 440 445 Lys Trp Ala Phe Thr Trp Pro Leu Ser Phe Val Leu Tyr Phe Thr Val 450 455 460 Pro Asn Cys Asn Lys Pro Arg Trp Glu Lys Trp Phe Met Val Thr Phe 465 470 475 480 Ala Ser Ser Thr Leu Trp Ile Ala Ala Phe Ser Tyr Met Met Val Trp 485 490 495 Met Val Thr Ile Ile Gly Tyr Thr Leu Gly Ile Pro Asp Val Ile Met 500 505 510 Gly Ile Thr Phe Leu Ala Ala Gly Thr Ser Val Pro Asp Cys Met Ala 515 520 525 Ser Leu Ile Val Ala Arg Gln Gly Met Gly Asp Met Ala Val Ser Asn 530 535 540 Ser Ile Gly Ser Asn Val Phe Asp Ile Leu Ile Gly Leu Gly Leu Pro 545 550 555 560 Trp Ala Leu Gln Thr Leu Ala Val Asp Tyr Gly Ser Tyr Ile Arg Leu 565 570 575 Asn Ser Arg Gly Leu Ile Tyr Ser Val Gly Leu Leu Leu Ala Ser Val 580 585 590 Phe Val Thr Val Phe Gly Val His Leu Asn Lys Trp Gln Leu Asp Lys 595 600 605 Lys Leu Gly Cys Gly Cys Leu Leu Leu Tyr Gly Val Phe Leu Cys Phe 610 615 620 Ser Ile Met Thr Glu Phe Asn Val Phe Thr Phe Val Asn Leu Pro Met 625 630 635 640 Cys Gly Asp His 19 1228 DNA Homo Sapiens misc_feature (1)...(1228) n = A,T,C or G 19 ttttggtcct tttaatttcc agggtcccgg nattccgggt gggtggtgca aatcaaaaaa 60 cttgctcctc cagtggaatg gtngcctttn actttctagg ccntggacgg aaagtgttac 120 cttctgcttt aaaaagcttg cggnaatttc ttaataccga cctcacctat agggaagtcg 180 gaccccacgg cgtccgccca attctctata ctctgaccac aagaccattt atcatcatag 240 ttttttccta tggaagcatg ttttatagtg ttcatcaaag tgccataaca gcaactgaaa 300 tacggaatca agttaaaaaa gagatgatcc ttgccaaacg ttttttcttt atagtattta 360 ctgatgcatt atgctggata cccatttttg tagtgaaatt tctttcactg cttcaggtag 420 aaataccagg taccataacc tcttgggtag tgatttttat tctgcccatt aacagtgctt 480 tgaacccaat tctctatact ctgaccacaa gaccatttaa agaaatgatt catcggtttt 540 ggtataacta cagacaaaga aaatctatgg acagcaaagg tcagaaaaca tatgctccat 600 cattcatctg ggtggaaatg tggccactgc aggagatgcc acctgagtta atgaagccgg 660 accttttcac atacccctgt gaaatgtcac tgatttctca atcaacgaga ctcaattcct 720 attcatgact gactctgaaa ttcatttctt cgcagagaat actgtggggg tgcttcatga 780 gggatttact ggtatgaaat gaatacccca aaattaattt ataataatag ctaagataaa 840 tattttacaa ggacatgagg aaaaataaaa atgactaatg ctcttacaaa gggaagtaat 900 tatatcaata atgtatatat attagtagac attttgcata agaaattaag agaaatctac 960 ttcagtaaca ttcattcatt tttctaacat gcatttattg agtacccact actatgtgca 1020 tagcattgca atatagtcct ggaagtagac agtgcagaac ctttcaatct gtagatggtg 1080 tttaatgaca aaagactata caaagtccat ctgcagttcc tagtttaaag tagagcttta 1140 cctgtcatgt gcatcagcaa gaatcatagg cacttttaaa taaaggttta aagttttgga 1200 aaaaaaaaaa aaaaaaaaaa aagggcgg 1228 20 216 PRT Homo Sapiens VARIANT (1)...(216) Xaa = Any Amino Acid 20 Met Val Ala Phe Xaa Phe Leu Gly Xaa Gly Arg Lys Val Leu Pro Ser 1 5 10 15 Ala Leu Lys Ser Leu Arg Xaa Phe Leu Asn Thr Asp Leu Thr Tyr Arg 20 25 30 Glu Val Gly Pro His Gly Val Arg Pro Ile Leu Tyr Thr Leu Thr Thr 35 40 45 Arg Pro Phe Ile Ile Ile Val Phe Ser Tyr Gly Ser Met Phe Tyr Ser 50 55 60 Val His Gln Ser Ala Ile Thr Ala Thr Glu Ile Arg Asn Gln Val Lys 65 70 75 80 Lys Glu Met Ile Leu Ala Lys Arg Phe Phe Phe Ile Val Phe Thr Asp 85 90 95 Ala Leu Cys Trp Ile Pro Ile Phe Val Val Lys Phe Leu Ser Leu Leu 100 105 110 Gln Val Glu Ile Pro Gly Thr Ile Thr Ser Trp Val Val Ile Phe Ile 115 120 125 Leu Pro Ile Asn Ser Ala Leu Asn Pro Ile Leu Tyr Thr Leu Thr Thr 130 135 140 Arg Pro Phe Lys Glu Met Ile His Arg Phe Trp Tyr Asn Tyr Arg Gln 145 150 155 160 Arg Lys Ser Met Asp Ser Lys Gly Gln Lys Thr Tyr Ala Pro Ser Phe 165 170 175 Ile Trp Val Glu Met Trp Pro Leu Gln Glu Met Pro Pro Glu Leu Met 180 185 190 Lys Pro Asp Leu Phe Thr Tyr Pro Cys Glu Met Ser Leu Ile Ser Gln 195 200 205 Ser Thr Arg Leu Asn Ser Tyr Ser 210 215 21 3371 DNA Homo Sapiens 21 aaaaaaccag gaagtgaagt ccccgagcac gttagaaagc ctgacatggc ctgactcggg 60 acagctcaga gcagggcaga actggggaca ctctgggccg gccttctgcc tgcatggacg 120 ctctgaagcc accctgtctc tggaggaacc acgagcgagg gaagaaggac agggactcgt 180 gtggcaggaa gaactcagag ccgggaagcc cccattcact agaagcactg agagatgcgg 240 ccccctcgca gggtctgaat ttcctgctgc tgttcacaaa gatgcttttt atctttaact 300 ttttgttttc cccacttccg accccggcgt tgatctgcat cctgacattt ggagctgcca 360 tcttcttgtg gctgatcacc agacctcaac ccgtcttacc tcttcttgac ctgaacaatc 420 agtctgtggg aattgaggga ggagcacgga agggggtttc ccagaagaac aatgacctaa 480 caagttgctg cttctcagat gccaagacta tgtatgaggt tttccaaaga ggactcgctg 540 tgtctgacaa tgggccctgc ttgggatata gaaaaccaaa ccagccctac agatggctat 600 cttacaaaca ggtgtctgat agagcagagt acctgggttc ctgtctcttg cataaaggtt 660 ataaatcatc accagaccag tttgtcggca tctttgctca gaataggcca gagtggatca 720 tctccgaatt ggcttgttac acgtactcta tggtagctgt acctctgtat gacaccttgg 780 gaccagaagc catcgtacat attgtcaaca aggctgatat cgccatggtg atctgtgaca 840 caccccaaaa ggcattggtg ctgataggga atgtagagaa aggcttcacc ccgagcctga 900 aggtgatcat ccttatggac ccctttgatg atgacctgaa gcaaagaggg gagaagagtg 960 gaattgagat cttatcccta tatgatgctg agaacctagg caaagagcac ttcagaaaac 1020 ctgtgcctcc tagcccagaa gacctgagcg tcatctgctt caccagtggg accacaggtg 1080 accccaaagg agccatgata acccatcaaa atattgtttc aaatgctgct gcctttctca 1140 aatgtgtgga gcatgcttat gagcccactc ctgatgatgt ggccatatcc tacctccctc 1200 tggctcatat gtttgagagg attgtacagg ctgttgtgta cagctgtgga gccagagttg 1260 gattcttcca aggggatatt cggttgctgg ctgacgacat gaagactttg aagcccacat 1320 tgtttcccgc ggtgcctcga ctccttaaca ggatctacga taaggtacaa aatgaggcca 1380 agacaccctt gaagaagttc ttgttgaagc tggctgtttc cagtaaattc aaagagcttc 1440 aaaagggtat catcaggcat gatagtttct gggacaagct catctttgca aagatccagg 1500 acagcctggg cggaagggtt cgtgtaattg tcactggagc tgcccccatg tccacttcag 1560 tcatgacatt cttccgggca gcaatgggat gtcaggtgta tgaagcttat ggtcaaacag 1620 aatgcacagg tggctgtaca tttacattac ctggggactg gacatcaggt cacgttgggg 1680 tgcccctggc ttgcaattac gtgaagctgg aagatgtggc tgacatgaac tactttacag 1740 tgaataatga aggagaggtc tgcatcaagg gtacaaacgt gttcaaagga tacctgaagg 1800 accctgagaa gacacaggaa gccctggaca gtgatggctg gcttcacaca ggagacattg 1860 gtcgctggct cccgaatgga actctgaaga tcatcgaccg taaaaagaac attttcaagc 1920 tggcccaagg agaatacatt gcaccagaga agatagaaaa tatctacaac aggagtcaac 1980 cagtgttaca aatttttgta cacggggaga gcttacggtc atccttagta ggagtggtgg 2040 ttcctgacac agatgtactt ccctcatttg cagccaagct tggggtgaag ggctcctttg 2100 aggaactgtg ccaaaaccaa gttgtaaggg aagccatttt agaagacttg cagaaaattg 2160 ggaaagaaag tggccttaaa acttttgaac aggtcaaagc catttttctt catccagagc 2220 cattttccat tgaaaatggg ctcttgacac caacattgaa agcaaagcga ggagagcttt 2280 ccaaatactt tcggacccaa attgacagcc tgtatgagca catccaggat taggataagg 2340 tacttaagta cctgccggcc cactgtgcac tgcttgtgag aaaatggatt aaaaactatt 2400 cttacatttg ttttgccttt cctcctattt ttttttaacc tgttaaactc taaagccata 2460 gcttttgttt tatattgaga catataatgt gtaaacttag ttcccaaata aatcaatcct 2520 gtctttccca tcttcgatgt tgctaatatt aaggcttcag ggctactttt atcaacatgc 2580 ctggcttcaa gatcccagtt tatgttctgt gtccttcctc atgatttcca accttaatac 2640 tattagtaac cacaagttca agggtcaaag ggaccctctg tgccttcttc tttgttttgt 2700 gataaacata acttgccaac agtctctatg cttatttaca tcttctactg ttcaaactaa 2760 gagattttta aattctgaaa aactgcttac aattcatgtt ttctagccac tccacaaacc 2820 actaaaattt tagttttagc ctatcactca tgtcaatcat atctatgaga caaatgtctc 2880 cgatgctctt ctgcgtaaat taaattgtgt actgaaggga aaagtttgat cataccaaac 2940 atttcctaaa ctctctagtt agatatctga cttgggagta ttaaaaattg ggtctatgac 3000 atattgtcca aaaggaatgc tgttcttaaa gcattattta cagtaggaac tggggagtaa 3060 atctgttccc tacagtttgc tgctgagctg gaagctgtgg gggaaggagt tgacaggtgg 3120 gcccagtgaa cttttccagt aaatgaagca agcactgaat aaaaacctcc tgaactggga 3180 acaaagatct acaggcaagc aagatgccca cacaacaggc ttattttctg tgaaggaacc 3240 aactgatctc ccccaccctt ggattagagt tcctgctcta ccttacccac agataacaca 3300 tgttgtttct acttgtaaat gtaaagtctt taaaataaac tattacagat acttaaaaaa 3360 aaaaaaaaaa a 3371 22 739 PRT Homo Sapiens 22 Met Asp Ala Leu Lys Pro Pro Cys Leu Trp Arg Asn His Glu Arg Gly 1 5 10 15 Lys Lys Asp Arg Asp Ser Cys Gly Arg Lys Asn Ser Glu Pro Gly Ser 20 25 30 Pro His Ser Leu Glu Ala Leu Arg Asp Ala Ala Pro Ser Gln Gly Leu 35 40 45 Asn Phe Leu Leu Leu Phe Thr Lys Met Leu Phe Ile Phe Asn Phe Leu 50 55 60 Phe Ser Pro Leu Pro Thr Pro Ala Leu Ile Cys Ile Leu Thr Phe Gly 65 70 75 80 Ala Ala Ile Phe Leu Trp Leu Ile Thr Arg Pro Gln Pro Val Leu Pro 85 90 95 Leu Leu Asp Leu Asn Asn Gln Ser Val Gly Ile Glu Gly Gly Ala Arg 100 105 110 Lys Gly Val Ser Gln Lys Asn Asn Asp Leu Thr Ser Cys Cys Phe Ser 115 120 125 Asp Ala Lys Thr Met Tyr Glu Val Phe Gln Arg Gly Leu Ala Val Ser 130 135 140 Asp Asn Gly Pro Cys Leu Gly Tyr Arg Lys Pro Asn Gln Pro Tyr Arg 145 150 155 160 Trp Leu Ser Tyr Lys Gln Val Ser Asp Arg Ala Glu Tyr Leu Gly Ser 165 170 175 Cys Leu Leu His Lys Gly Tyr Lys Ser Ser Pro Asp Gln Phe Val Gly 180 185 190 Ile Phe Ala Gln Asn Arg Pro Glu Trp Ile Ile Ser Glu Leu Ala Cys 195 200 205 Tyr Thr Tyr Ser Met Val Ala Val Pro Leu Tyr Asp Thr Leu Gly Pro 210 215 220 Glu Ala Ile Val His Ile Val Asn Lys Ala Asp Ile Ala Met Val Ile 225 230 235 240 Cys Asp Thr Pro Gln Lys Ala Leu Val Leu Ile Gly Asn Val Glu Lys 245 250 255 Gly Phe Thr Pro Ser Leu Lys Val Ile Ile Leu Met Asp Pro Phe Asp 260 265 270 Asp Asp Leu Lys Gln Arg Gly Glu Lys Ser Gly Ile Glu Ile Leu Ser 275 280 285 Leu Tyr Asp Ala Glu Asn Leu Gly Lys Glu His Phe Arg Lys Pro Val 290 295 300 Pro Pro Ser Pro Glu Asp Leu Ser Val Ile Cys Phe Thr Ser Gly Thr 305 310 315 320 Thr Gly Asp Pro Lys Gly Ala Met Ile Thr His Gln Asn Ile Val Ser 325 330 335 Asn Ala Ala Ala Phe Leu Lys Cys Val Glu His Ala Tyr Glu Pro Thr 340 345 350 Pro Asp Asp Val Ala Ile Ser Tyr Leu Pro Leu Ala His Met Phe Glu 355 360 365 Arg Ile Val Gln Ala Val Val Tyr Ser Cys Gly Ala Arg Val Gly Phe 370 375 380 Phe Gln Gly Asp Ile Arg Leu Leu Ala Asp Asp Met Lys Thr Leu Lys 385 390 395 400 Pro Thr Leu Phe Pro Ala Val Pro Arg Leu Leu Asn Arg Ile Tyr Asp 405 410 415 Lys Val Gln Asn Glu Ala Lys Thr Pro Leu Lys Lys Phe Leu Leu Lys 420 425 430 Leu Ala Val Ser Ser Lys Phe Lys Glu Leu Gln Lys Gly Ile Ile Arg 435 440 445 His Asp Ser Phe Trp Asp Lys Leu Ile Phe Ala Lys Ile Gln Asp Ser 450 455 460 Leu Gly Gly Arg Val Arg Val Ile Val Thr Gly Ala Ala Pro Met Ser 465 470 475 480 Thr Ser Val Met Thr Phe Phe Arg Ala Ala Met Gly Cys Gln Val Tyr 485 490 495 Glu Ala Tyr Gly Gln Thr Glu Cys Thr Gly Gly Cys Thr Phe Thr Leu 500 505 510 Pro Gly Asp Trp Thr Ser Gly His Val Gly Val Pro Leu Ala Cys Asn 515 520 525 Tyr Val Lys Leu Glu Asp Val Ala Asp Met Asn Tyr Phe Thr Val Asn 530 535 540 Asn Glu Gly Glu Val Cys Ile Lys Gly Thr Asn Val Phe Lys Gly Tyr 545 550 555 560 Leu Lys Asp Pro Glu Lys Thr Gln Glu Ala Leu Asp Ser Asp Gly Trp 565 570 575 Leu His Thr Gly Asp Ile Gly Arg Trp Leu Pro Asn Gly Thr Leu Lys 580 585 590 Ile Ile Asp Arg Lys Lys Asn Ile Phe Lys Leu Ala Gln Gly Glu Tyr 595 600 605 Ile Ala Pro Glu Lys Ile Glu Asn Ile Tyr Asn Arg Ser Gln Pro Val 610 615 620 Leu Gln Ile Phe Val His Gly Glu Ser Leu Arg Ser Ser Leu Val Gly 625 630 635 640 Val Val Val Pro Asp Thr Asp Val Leu Pro Ser Phe Ala Ala Lys Leu 645 650 655 Gly Val Lys Gly Ser Phe Glu Glu Leu Cys Gln Asn Gln Val Val Arg 660 665 670 Glu Ala Ile Leu Glu Asp Leu Gln Lys Ile Gly Lys Glu Ser Gly Leu 675 680 685 Lys Thr Phe Glu Gln Val Lys Ala Ile Phe Leu His Pro Glu Pro Phe 690 695 700 Ser Ile Glu Asn Gly Leu Leu Thr Pro Thr Leu Lys Ala Lys Arg Gly 705 710 715 720 Glu Leu Ser Lys Tyr Phe Arg Thr Gln Ile Asp Ser Leu Tyr Glu His 725 730 735 Ile Gln Asp 23 1734 DNA Homo Sapiens 23 ggcacgaggc gccgggccat gggcctcgag cccgccccga acccccgcga gcccgccttg 60 tctgcggcgt gactggaggc ccagatggtc atcatgggcc agtgctacta caacgagacc 120 atcggcttct tctataacaa cagtggcaaa gagctcagct cccactggcg gcccaaggat 180 gtggtcgtgg tggcactggg gctgaccgtc agcgtgctgg tgctgctgac caatctgctg 240 gtcatagcag ccatcgcctc caaccgccgc ttccaccagc ccatctacta cctgctcggc 300 aatctggccg cggctgacct cttcgcgggc gtggcctacc tcttcctcat gttccacact 360 ggtccccgca cagcccgact ttcacttgag ggctggttcc tgcggcaggg cttgctggac 420 acaagcctca ctgcgtcggt ggccacactg ctggccatcg ccgtggagcg gcaccgcagt 480 gtgatggccg tgcagctgca cagccgcctg ccccgtggcc gcgtggtcat gctcattgtg 540 ggcgtgtggg tggctgccct gggcctgggg ctgctgcctg cccactcctg gcactgcctc 600 tgtgccctgg accgctgctc acgcatggca cccctgctca gccgctccta tttggccgtc 660 tgggctctgt cgagcctgct tgtcttcctg ctcatggtgg ctgtgtacac ccgcattttc 720 ttctacgtgc ggcggcgagt gcagcgcatg gcagagcatg tcagctgcca cccccgctac 780 cgagagacca cgctcagcct ggtcaagact gttgtcatca tcctgggggc gttcgtggtc 840 tgctggacac caggccaggt ggtactgctc ctggatggtt taggctgtga gtcctgcaat 900 gtcctggctg tagaaaagta cttcctactg ttggccgagg ccaactcact ggtcaatgct 960 gctgtgtact cttgccgaga tgctgagatg cgccgcacct tccgccgcct tctctgctgc 1020 gcgtgcctcc gccagtccac ccgcgagtct gtccactata catcctctgc ccagggaggt 1080 gccagcactc gcatcatgct tcccgagaac ggccacccac tgatgactcc accctttagc 1140 taccttgaac ttcagcggta cgcggcaagc aacaaatcca cagcccctga tgacttgtgg 1200 gtgctcctgg ctcaacccaa ccaacaggac tgactgactg gcaggacaag gtctggcatg 1260 gcacagcacc actgccaggc ctccccaggc acaccactct gcccagggaa tgggggcttt 1320 gggtcatctc ccactgcctg ggggagtcag atggggtgca ggaatctggc tcttcagcca 1380 tctcaggttt agggggtttg taacagacat tattctgttt tcactgcgta tccttggtaa 1440 gccctgtgga ctggttcctg ctgtgtgatg ctgagggttt taaggtgggg agagataagg 1500 gctctctcgg gccatgctac ccggtatgac tgggtaatga ggacagactg tggacacccc 1560 atctacctga gtctgattct ttagcagcag agactgaggg gtgcagagtg tgagctggga 1620 aaggtttgtg gctccttgca gcctccaggg actggcctgt ccccaataga attgaagcag 1680 tccacgggga ggggatgata caaggagtaa acctttcttt acactcaaaa aaaa 1734 24 382 PRT Homo Sapiens 24 Met Val Ile Met Gly Gln Cys Tyr Tyr Asn Glu Thr Ile Gly Phe Phe 1 5 10 15 Tyr Asn Asn Ser Gly Lys Glu Leu Ser Ser His Trp Arg Pro Lys Asp 20 25 30 Val Val Val Val Ala Leu Gly Leu Thr Val Ser Val Leu Val Leu Leu 35 40 45 Thr Asn Leu Leu Val Ile Ala Ala Ile Ala Ser Asn Arg Arg Phe His 50 55 60 Gln Pro Ile Tyr Tyr Leu Leu Gly Asn Leu Ala Ala Ala Asp Leu Phe 65 70 75 80 Ala Gly Val Ala Tyr Leu Phe Leu Met Phe His Thr Gly Pro Arg Thr 85 90 95 Ala Arg Leu Ser Leu Glu Gly Trp Phe Leu Arg Gln Gly Leu Leu Asp 100 105 110 Thr Ser Leu Thr Ala Ser Val Ala Thr Leu Leu Ala Ile Ala Val Glu 115 120 125 Arg His Arg Ser Val Met Ala Val Gln Leu His Ser Arg Leu Pro Arg 130 135 140 Gly Arg Val Val Met Leu Ile Val Gly Val Trp Val Ala Ala Leu Gly 145 150 155 160 Leu Gly Leu Leu Pro Ala His Ser Trp His Cys Leu Cys Ala Leu Asp 165 170 175 Arg Cys Ser Arg Met Ala Pro Leu Leu Ser Arg Ser Tyr Leu Ala Val 180 185 190 Trp Ala Leu Ser Ser Leu Leu Val Phe Leu Leu Met Val Ala Val Tyr 195 200 205 Thr Arg Ile Phe Phe Tyr Val Arg Arg Arg Val Gln Arg Met Ala Glu 210 215 220 His Val Ser Cys His Pro Arg Tyr Arg Glu Thr Thr Leu Ser Leu Val 225 230 235 240 Lys Thr Val Val Ile Ile Leu Gly Ala Phe Val Val Cys Trp Thr Pro 245 250 255 Gly Gln Val Val Leu Leu Leu Asp Gly Leu Gly Cys Glu Ser Cys Asn 260 265 270 Val Leu Ala Val Glu Lys Tyr Phe Leu Leu Leu Ala Glu Ala Asn Ser 275 280 285 Leu Val Asn Ala Ala Val Tyr Ser Cys Arg Asp Ala Glu Met Arg Arg 290 295 300 Thr Phe Arg Arg Leu Leu Cys Cys Ala Cys Leu Arg Gln Ser Thr Arg 305 310 315 320 Glu Ser Val His Tyr Thr Ser Ser Ala Gln Gly Gly Ala Ser Thr Arg 325 330 335 Ile Met Leu Pro Glu Asn Gly His Pro Leu Met Thr Pro Pro Phe Ser 340 345 350 Tyr Leu Glu Leu Gln Arg Tyr Ala Ala Ser Asn Lys Ser Thr Ala Pro 355 360 365 Asp Asp Leu Trp Val Leu Leu Ala Gln Pro Asn Gln Gln Asp 370 375 380 25 277 DNA Homo Sapiens 25 ggggcgggcc aagcgtgacc gcgggtcggc ggggcgtgtt taagaccgcg gcgtgcgctc 60 ccggcccacg ccagctccgg ccgcggcaca gcagccccgg cgctccccgc gccgccccgc 120 gcaggcgccc ccgccccgcc gtcgccgccg ccgcagccag gagccgctgc accatgcccc 180 gcatagatgc ggacctcaag ctcgacttca aggatgtcct gctccgacct aagcggagca 240 gcctcaagag ccgagccgag gtggggagct tcggaag 277 26 29 PRT Homo Sapiens 26 Met Pro Arg Ile Asp Ala Asp Leu Lys Leu Asp Phe Lys Asp Val Leu 1 5 10 15 Leu Arg Pro Lys Arg Ser Ser Leu Lys Ser Arg Ala Glu 20 25 27 3151 DNA Homo Sapiens 27 ttttccttga gcacagcact ttgtgacctt tgatgtaaac atcaaacaca gccccctttc 60 ctgtcttcgc atccaggaaa taggttagtt tcagacaagc ctgcttgccg gagctcagca 120 gacaccaggc cttccgggca ggcctggccc accgtgggcc tcagagctgc tgctggggca 180 ttcagaaccg gctctccatt ggcattggga ccagagaccc cgcaagtggc ctgtttgcct 240 ggacatccac ctgtacgtcc ccaggtttcg ggaggcccag gggcgatgcc agaccccgcg 300 gcgcacctgc ccttcttcta cggcagcatc tcgcgtgccg aggccgagga gcacctgaag 360 ctggcgggca tggcggacgg gctcttcctg ctgcgccagt gcctgcgctc gctgggcggc 420 tatgtgctgt cgctcgtgca cgatgtgcgc ttccaccact ttcccatcga gcgccagctc 480 aacggcacct acgccattgc cggcggcaaa gcgcactgtg gaccggcaga gctctgcgag 540 ttctactcgc gcgaccccga cgggctgccc tgcaacctgc gcaagccgtg caaccggccg 600 tcgggcctcg agccgcagcc gggggtcttc gactgcctgc gagacgccat ggtgcgtgac 660 tacgtgcgcc agacgtggaa gctggagggc gaggccctgg agcaggccat catcagccag 720 gccccgcagg tggagaagct cattgctacg acggcccacg agcggatgcc ctggtaccac 780 agcagcctga cgcgtgagga ggccgagcgc aaactttact ctggggcgca gaccgacggc 840 aagttcctgc tgaggccgcg gaaggagcag ggcacatacg ccctgtccct catctatggg 900 aagacggtgt accactacct catcagccaa gacaaggcgg gcaagtactg cattcccgag 960 ggcaccaagt ttgacacgct ctggcagctg gtggagtatc tgaagctgaa ggcggacggg 1020 ctcatctact gcctgaagga ggcctgcccc aacagcagtg ccagcaacgc ctcaggggct 1080 gctgctccca cactcccagc ccacccatcc acgttgactc atcctcagag acgaatcgac 1140 accctcaact cagatggata cacccctgag ccagcacgca taacgtcccc agacaaaccg 1200 cggccgatgc ccatggacac gagcgtgtat gagagcccct acagcgaccc agaggagctc 1260 aaggacaaga agctcttcct gaagcgcgat aacctcctca tagctgacat tgaacttggc 1320 tgcggcaact ttggctcagt gcgccagggc gtgtaccgca tgcgcaagaa gcagatcgac 1380 gtggccatca aggtgctgaa gcagggcacg gagaaggcag acacggaaga gatgatgcgc 1440 gaggcgcaga tcatgcacca gctggacaac ccctacatcg tgcggctcat tggcgtctgc 1500 caggccgagg ccctcatgct ggtcatggag atggctgggg gcgggccgct gcacaagttc 1560 ctggtcggca agagggagga gatccctgtg agcaatgtgg ccgagctgct gcaccaggtg 1620 tccatgggga tgaagtacct ggaggagaag aactttgtgc accgtgacct ggcggcccgc 1680 aacgtcctgc tggttaaccg gcactacgcc aagatcagcg actttggcct ctccaaagca 1740 ctgggtgccg acgacagcta ctacactgcc cgctcagcag ggaagtggcc gctcaagtgg 1800 tacgcacccg aatgcatcaa cttccgcaag ttctccagcc gcagcgatgt ctggagctat 1860 ggggtcacca tgtgggaggc cttgtcctac ggccagaagc cctacaagaa gatgaaaggg 1920 ccggaggtca tggccttcat cgagcagggc aagcggatgg agtgcccacc agagtgtcca 1980 cccgaactgt acgcactcat gagtgactgc tggatctaca agtgggagga tcgccccgac 2040 ttcctgaccg tggagcagcg catgcgagcc tgttactaca gcctggccag caaggtggaa 2100 gggcccccag gcagcacaca gaaggctgag gctgcctgtg cctgagctcc cgctgcccag 2160 gggagccctc cacgccggct cttccccacc ctcagcccca ccccaggtcc tgcagtctgg 2220 ctgagccctg cttggttgtc tccacacaca gctgggctgt ggtagggggt gtctcaggcc 2280 acaccggcct tgcattgcct gcctggcccc ctgtcctctc tggctgggga gcagggaggt 2340 ccgggagggt gcggctgtgc agcctgtcct gggctggtgg ctcccggagg gccctgagct 2400 gagggcattg cttacacgga tgccttcccc tgggccctga cattggagcc tgggcatcct 2460 caggtggtca ggcgtagatc accagaataa acccagcttc cctcttgtct gagcgccctc 2520 atcttttccg gggtgagggt aggtgtcagg ggaggggtgg gttatgaaaa gtgcatggag 2580 gtgactgttc ttgtgtggac tgagcctgga agtgacccct gggaagatgg ggctgggtcc 2640 cactctccac cctagggaca ccttcatgtg agtgagcggc tggggtggag tggcgaacct 2700 gacgccaggc gggtgtgggc ccaagggctg cgtgcctggc tgagcccagc tcccctgtgt 2760 ggagatgagt gtgccccatg ccaggtgcac gttaggatca cctggagcta ttttaacaaa 2820 cgctaacccc ccctccccca tccagctggg gtcttcaccc cccaggggtg ccttgcaaat 2880 catgagatac aatgcttttc attggtagat gcacgtatta gctcccgtat gaaccgtatt 2940 actgaatttg aatctgaaaa ataccaaaat gcaaacattg tttttaaatt aattgtttta 3000 aaagctaatg aacgaattaa gacaaattgc atcaatttag tggtttctta aatcgtggtt 3060 tgcaggtagt tcagttttat taaaattcat ttgtgagtcg ctgaacgact tacattatgt 3120 aaaatatatc agacagtaaa tgaattgtgg c 3151 28 619 PRT Homo Sapiens 28 Met Pro Asp Pro Ala Ala His Leu Pro Phe Phe Tyr Gly Ser Ile Ser 1 5 10 15 Arg Ala Glu Ala Glu Glu His Leu Lys Leu Ala Gly Met Ala Asp Gly 20 25 30 Leu Phe Leu Leu Arg Gln Cys Leu Arg Ser Leu Gly Gly Tyr Val Leu 35 40 45 Ser Leu Val His Asp Val Arg Phe His His Phe Pro Ile Glu Arg Gln 50 55 60 Leu Asn Gly Thr Tyr Ala Ile Ala Gly Gly Lys Ala His Cys Gly Pro 65 70 75 80 Ala Glu Leu Cys Glu Phe Tyr Ser Arg Asp Pro Asp Gly Leu Pro Cys 85 90 95 Asn Leu Arg Lys Pro Cys Asn Arg Pro Ser Gly Leu Glu Pro Gln Pro 100 105 110 Gly Val Phe Asp Cys Leu Arg Asp Ala Met Val Arg Asp Tyr Val Arg 115 120 125 Gln Thr Trp Lys Leu Glu Gly Glu Ala Leu Glu Gln Ala Ile Ile Ser 130 135 140 Gln Ala Pro Gln Val Glu Lys Leu Ile Ala Thr Thr Ala His Glu Arg 145 150 155 160 Met Pro Trp Tyr His Ser Ser Leu Thr Arg Glu Glu Ala Glu Arg Lys 165 170 175 Leu Tyr Ser Gly Ala Gln Thr Asp Gly Lys Phe Leu Leu Arg Pro Arg 180 185 190 Lys Glu Gln Gly Thr Tyr Ala Leu Ser Leu Ile Tyr Gly Lys Thr Val 195 200 205 Tyr His Tyr Leu Ile Ser Gln Asp Lys Ala Gly Lys Tyr Cys Ile Pro 210 215 220 Glu Gly Thr Lys Phe Asp Thr Leu Trp Gln Leu Val Glu Tyr Leu Lys 225 230 235 240 Leu Lys Ala Asp Gly Leu Ile Tyr Cys Leu Lys Glu Ala Cys Pro Asn 245 250 255 Ser Ser Ala Ser Asn Ala Ser Gly Ala Ala Ala Pro Thr Leu Pro Ala 260 265 270 His Pro Ser Thr Leu Thr His Pro Gln Arg Arg Ile Asp Thr Leu Asn 275 280 285 Ser Asp Gly Tyr Thr Pro Glu Pro Ala Arg Ile Thr Ser Pro Asp Lys 290 295 300 Pro Arg Pro Met Pro Met Asp Thr Ser Val Tyr Glu Ser Pro Tyr Ser 305 310 315 320 Asp Pro Glu Glu Leu Lys Asp Lys Lys Leu Phe Leu Lys Arg Asp Asn 325 330 335 Leu Leu Ile Ala Asp Ile Glu Leu Gly Cys Gly Asn Phe Gly Ser Val 340 345 350 Arg Gln Gly Val Tyr Arg Met Arg Lys Lys Gln Ile Asp Val Ala Ile 355 360 365 Lys Val Leu Lys Gln Gly Thr Glu Lys Ala Asp Thr Glu Glu Met Met 370 375 380 Arg Glu Ala Gln Ile Met His Gln Leu Asp Asn Pro Tyr Ile Val Arg 385 390 395 400 Leu Ile Gly Val Cys Gln Ala Glu Ala Leu Met Leu Val Met Glu Met 405 410 415 Ala Gly Gly Gly Pro Leu His Lys Phe Leu Val Gly Lys Arg Glu Glu 420 425 430 Ile Pro Val Ser Asn Val Ala Glu Leu Leu His Gln Val Ser Met Gly 435 440 445 Met Lys Tyr Leu Glu Glu Lys Asn Phe Val His Arg Asp Leu Ala Ala 450 455 460 Arg Asn Val Leu Leu Val Asn Arg His Tyr Ala Lys Ile Ser Asp Phe 465 470 475 480 Gly Leu Ser Lys Ala Leu Gly Ala Asp Asp Ser Tyr Tyr Thr Ala Arg 485 490 495 Ser Ala Gly Lys Trp Pro Leu Lys Trp Tyr Ala Pro Glu Cys Ile Asn 500 505 510 Phe Arg Lys Phe Ser Ser Arg Ser Asp Val Trp Ser Tyr Gly Val Thr 515 520 525 Met Trp Glu Ala Leu Ser Tyr Gly Gln Lys Pro Tyr Lys Lys Met Lys 530 535 540 Gly Pro Glu Val Met Ala Phe Ile Glu Gln Gly Lys Arg Met Glu Cys 545 550 555 560 Pro Pro Glu Cys Pro Pro Glu Leu Tyr Ala Leu Met Ser Asp Cys Trp 565 570 575 Ile Tyr Lys Trp Glu Asp Arg Pro Asp Phe Leu Thr Val Glu Gln Arg 580 585 590 Met Arg Ala Cys Tyr Tyr Ser Leu Ala Ser Lys Val Glu Gly Pro Pro 595 600 605 Gly Ser Thr Gln Lys Ala Glu Ala Ala Cys Ala 610 615 29 1808 DNA Homo Sapiens 29 gcctagtccc gcccctgcgt gcggcgcttc tcccaggccc caccttccat ccagtgccct 60 ggaccctcgg ctgggtagcg ccaccagagc gaccaaacgt cccgcgcctt ccaggccgca 120 ctccagagcc aaaagagctc catggcggcg gcggccaagc ccaacaacct ttccctggtg 180 gtgcacggac cgggggactt gcgcctggag aactatccta tccctgaacc aggcccaaat 240 gaggtcttgc tgaggatgca ttctgttgga atctgtggct cagatgtcca ctactgggag 300 tatggtcgaa ttgggaattt tattgtgaaa aagcccatgg tgctgggaca tgaagcttcg 360 ggaacagtcg aaaaagtggg atcatcggta aagcacctaa aaccaggtga tcgtgttgcc 420 atcgagcctg gtgctccccg agaaaatgat gaattctgca agatgggccg atacaatctg 480 tcaccttcca tcttcttctg tgccacgccc cccgatgacg ggaacctctg ccggttctat 540 aagcacaatg cagccttttg ttacaagctt cctgacaatg tcacctttga ggaaggcgcc 600 ctgatcgagc cactttctgt ggggatccat gcctgcagga gaggcggagt taccctggga 660 cacaaggtcc ttgtgtgtgg agctgggcca atcgggatgg tcactttgct cgtggccaaa 720 gcaatgggag cagctcaagt agtggtgact gatctgtctg ctacccgatt gtccaaagcc 780 aaggagattg gggctgattt agtcctccag atctccaagg agagccctca ggaaatcgcc 840 aggaaagtag aaggtcagct ggggtgcaag ccggaagtca ccatcgagtg cacgggggca 900 gaggcctcca tccaggcggg catctacgcc actcgctctg gtgggaccct cgtgcttgtg 960 gggctgggct ctgagatgac caccgtaccc ctactgcatg cagccatccg ggaggtggat 1020 atcaagggcg tgtttcgata ctgcaacacg tggccagtgg cgatttcgat gcttgcgtcc 1080 aagtctgtga atgtaaaacc cctcgtcacc cataggtttc ctctggagaa agctctggag 1140 gcctttgaaa catttaaaaa gggattgggg ttgaaaatca tgctcaagtg tgaccccagt 1200 gaccagaatc cctgatgtta atgggctctg ctcatcccca cagtcttggg atctcagggc 1260 acaatggctg gacatgggtg ggctctgatg cagaactttc tcttttgaat gttaagaata 1320 actaatacaa ttcattgtga acagaagtcc ttaagcagag gaattggtgt gccttaaaga 1380 tacaatctgg gatagtttgg gggaacttgt agccagaatg ccctgttcat gctgagcaaa 1440 gttcagcaag tagagcagag tttggcaggc aggtgccagg aactcccctt cttcctggag 1500 tgccttcatt gaggaaggaa atctggccct tgggtttcct ggttccactg ctactgaccc 1560 agaggggaat gagggctgag ttatgaaaag ataacttcat gaagacttaa ctggcccaga 1620 agctgatttt catgaaaatc tgccactcag ggtctgggat gaaggcttgt cagcacttcc 1680 agtttagaac gcaatgtttc tagagacata ttggctgttt gttttgatga taaaaggaga 1740 ataagaaaag gcatcacttt cctggatcca ggataatttt taaaccaatc aaatgaaaaa 1800 aacaaaca 1808 30 357 PRT Homo Sapiens 30 Met Ala Ala Ala Ala Lys Pro Asn Asn Leu Ser Leu Val Val His Gly 1 5 10 15 Pro Gly Asp Leu Arg Leu Glu Asn Tyr Pro Ile Pro Glu Pro Gly Pro 20 25 30 Asn Glu Val Leu Leu Arg Met His Ser Val Gly Ile Cys Gly Ser Asp 35 40 45 Val His Tyr Trp Glu Tyr Gly Arg Ile Gly Asn Phe Ile Val Lys Lys 50 55 60 Pro Met Val Leu Gly His Glu Ala Ser Gly Thr Val Glu Lys Val Gly 65 70 75 80 Ser Ser Val Lys His Leu Lys Pro Gly Asp Arg Val Ala Ile Glu Pro 85 90 95 Gly Ala Pro Arg Glu Asn Asp Glu Phe Cys Lys Met Gly Arg Tyr Asn 100 105 110 Leu Ser Pro Ser Ile Phe Phe Cys Ala Thr Pro Pro Asp Asp Gly Asn 115 120 125 Leu Cys Arg Phe Tyr Lys His Asn Ala Ala Phe Cys Tyr Lys Leu Pro 130 135 140 Asp Asn Val Thr Phe Glu Glu Gly Ala Leu Ile Glu Pro Leu Ser Val 145 150 155 160 Gly Ile His Ala Cys Arg Arg Gly Gly Val Thr Leu Gly His Lys Val 165 170 175 Leu Val Cys Gly Ala Gly Pro Ile Gly Met Val Thr Leu Leu Val Ala 180 185 190 Lys Ala Met Gly Ala Ala Gln Val Val Val Thr Asp Leu Ser Ala Thr 195 200 205 Arg Leu Ser Lys Ala Lys Glu Ile Gly Ala Asp Leu Val Leu Gln Ile 210 215 220 Ser Lys Glu Ser Pro Gln Glu Ile Ala Arg Lys Val Glu Gly Gln Leu 225 230 235 240 Gly Cys Lys Pro Glu Val Thr Ile Glu Cys Thr Gly Ala Glu Ala Ser 245 250 255 Ile Gln Ala Gly Ile Tyr Ala Thr Arg Ser Gly Gly Thr Leu Val Leu 260 265 270 Val Gly Leu Gly Ser Glu Met Thr Thr Val Pro Leu Leu His Ala Ala 275 280 285 Ile Arg Glu Val Asp Ile Lys Gly Val Phe Arg Tyr Cys Asn Thr Trp 290 295 300 Pro Val Ala Ile Ser Met Leu Ala Ser Lys Ser Val Asn Val Lys Pro 305 310 315 320 Leu Val Thr His Arg Phe Pro Leu Glu Lys Ala Leu Glu Ala Phe Glu 325 330 335 Thr Phe Lys Lys Gly Leu Gly Leu Lys Ile Met Leu Lys Cys Asp Pro 340 345 350 Ser Asp Gln Asn Pro 355 31 2682 DNA Homo Sapiens 31 cacgccttgt ggcggctttg cggagctgct gctttggcgg gagttggaag ctggtgtgag 60 gtttctgtgg ggagaaggag agtgccagag gtgactggtt catggttctt ctaggctctc 120 atggccacca tgttggaagg cagatgccaa actcagccaa ggagcagccc cagtggccga 180 gaggctagcc tgtggtcgtc aggctttggg atgaagctgg aggctgtcac tccattcctg 240 gggaagtatc gcccctttgt gggtcgctgt tgccagacct gcacccccaa gagctgggag 300 tccctcttcc acagaagcat aacggaccta ggcttctgca atgtgatcct ggtgaaggag 360 gagaacacaa ggtttcgggg ctggctggtt cggaggctct gctatttcct gtggtccctg 420 gagcagcaca tccccccctg ccaggatgtc ccacagaaga tcatggaaag caccggggtg 480 cagaacctcc tctcagggag ggtcccagga ggcactgggg aaggccaggt gcctgacctt 540 gtgaagaagg aggtacagcg catcctgggt cacatccagg ccccaccccg tcccttcctg 600 gtcaggctgt tcagctgggc gctgctgagg ttcctgaact gcctgttcct gaatgtgcag 660 ctccacaagg gtcagatgaa gatggtccag aaggccgccc aggcaggctt gccgcttgtc 720 ctcctctcta ctcacaaaac cctcctggat gggatcctgc tgccctttat gctgctctcc 780 cagggcctgg gtgtgcttcg tgtggcctgg gactcccgcg cctgctcccc tgccctcaga 840 gctctgctga ggaagcttgg ggggcttttc ctgcccccag aggccagcct ctccctggac 900 agctctgagg ggctccttgc cagggctgtg gtccaggcgg tcatagagca gctgctggtt 960 agtgggcagc ccctgctcat cttcctggag gaacctcctg gggctctggg gccacggctg 1020 tcagccctgg gccaggcttg ggtggggttt gtggtgcagg cagtccaggt gggcatcgtc 1080 ccagatgctc tgctggtacc agtggccgtc acctatgacc tggttccgga tgcaccgtgt 1140 gacatagacc atgcctcggc ccccctgggg ctgtggacag gagctctggc tgtcctacgt 1200 agcttgtgga gccgctgggg ctgcagccac cggatctgct cccgggtgca cctagctcag 1260 cccttttccc tgcaggaata catcgtcagt gccagaagct gctggggcgg cagacagacc 1320 ctggagcagc tactgcagcc catcgtgctg ggccaatgta ctgctgtccc agacactgag 1380 aaggagcagg agtggacccc cataactggg cctctcctgg ccctcaagga agaggaccag 1440 ctcctggtca ggagactgag ctgtcatgtc ctgagtgcca gtgtagggag ctctgcggtg 1500 atgagcacgg ccattatggc aacgctgctg ctcttcaagc atcagaaggg tgtgttcctg 1560 tcgcagctcc tgggggagtt ctcctggctg acggaggaga tactgttgcg tggctttgat 1620 gtaggcttct ctgggcagct gcggagcctg ctgcagcact cactgagcct gctgcgggcg 1680 cacgtggccc tgctgcgcat ccgtcagggt gacttgctgg tggtgccgca gcctggccca 1740 ggcctcacac acctggcaca actgagtgct gagctgctgc ccgtcttcct gagcgaggct 1800 gtgggcgcct gtgcagtgcg ggggctgctg gcaggcagag tgccgcccca ggggccctgg 1860 gagctgcagg gcatattgct gctgagccag aatgagctgt accgccagat cctgctgctg 1920 atgcacctgc tgccgcaaga cctgctgctg ctaaagaccc caggctcccg gccagcctgt 1980 gacacagggc gacagcgatt gagcagaaag ctgctgtgga aaccgagtgg ggactttact 2040 gatagtgaca gtgatgactt cggagaggct gacggccggt acttcaggct cagccagcag 2100 tcacactgcc cagatttctt tcttttcctc tgccgcctgc tcagcccgct gctcaaggcc 2160 tttgcacagg ctgccgcctt cctccgccag ggccagctgc ccgatactga gttgggctac 2220 acagagcagc tgttccagtt cctgcaggcc accgcccagg aagaagggat cttcgagtgt 2280 gcggacccaa agctcgccat cagtgctgtc tggaccttca gagacctagg ggttctgcag 2340 cagacgccga gccctgcagg ccccaggctc cacctgtccc ctacttttgc cagcctggac 2400 aatcaggaaa aactagaaca gttcatccgg cagttcattt gtagctagaa ctgtgaggag 2460 gagcctgtgc tgagacttct cagccccaga acacagctgt gtcctagagc cagaagatgg 2520 agaggaggct gcaaaccctt agctgctcta taaatataat cattgaggct tgattgtccc 2580 ttgccatctc ttgctttttc ccttctttga tgtgataaac aaggggacga gacgagttgt 2640 cttttcccca gcccagcagc aaaaaaaaaa aaaaaaaaaa aa 2682 32 775 PRT Homo Sapiens 32 Met Ala Thr Met Leu Glu Gly Arg Cys Gln Thr Gln Pro Arg Ser Ser 1 5 10 15 Pro Ser Gly Arg Glu Ala Ser Leu Trp Ser Ser Gly Phe Gly Met Lys 20 25 30 Leu Glu Ala Val Thr Pro Phe Leu Gly Lys Tyr Arg Pro Phe Val Gly 35 40 45 Arg Cys Cys Gln Thr Cys Thr Pro Lys Ser Trp Glu Ser Leu Phe His 50 55 60 Arg Ser Ile Thr Asp Leu Gly Phe Cys Asn Val Ile Leu Val Lys Glu 65 70 75 80 Glu Asn Thr Arg Phe Arg Gly Trp Leu Val Arg Arg Leu Cys Tyr Phe 85 90 95 Leu Trp Ser Leu Glu Gln His Ile Pro Pro Cys Gln Asp Val Pro Gln 100 105 110 Lys Ile Met Glu Ser Thr Gly Val Gln Asn Leu Leu Ser Gly Arg Val 115 120 125 Pro Gly Gly Thr Gly Glu Gly Gln Val Pro Asp Leu Val Lys Lys Glu 130 135 140 Val Gln Arg Ile Leu Gly His Ile Gln Ala Pro Pro Arg Pro Phe Leu 145 150 155 160 Val Arg Leu Phe Ser Trp Ala Leu Leu Arg Phe Leu Asn Cys Leu Phe 165 170 175 Leu Asn Val Gln Leu His Lys Gly Gln Met Lys Met Val Gln Lys Ala 180 185 190 Ala Gln Ala Gly Leu Pro Leu Val Leu Leu Ser Thr His Lys Thr Leu 195 200 205 Leu Asp Gly Ile Leu Leu Pro Phe Met Leu Leu Ser Gln Gly Leu Gly 210 215 220 Val Leu Arg Val Ala Trp Asp Ser Arg Ala Cys Ser Pro Ala Leu Arg 225 230 235 240 Ala Leu Leu Arg Lys Leu Gly Gly Leu Phe Leu Pro Pro Glu Ala Ser 245 250 255 Leu Ser Leu Asp Ser Ser Glu Gly Leu Leu Ala Arg Ala Val Val Gln 260 265 270 Ala Val Ile Glu Gln Leu Leu Val Ser Gly Gln Pro Leu Leu Ile Phe 275 280 285 Leu Glu Glu Pro Pro Gly Ala Leu Gly Pro Arg Leu Ser Ala Leu Gly 290 295 300 Gln Ala Trp Val Gly Phe Val Val Gln Ala Val Gln Val Gly Ile Val 305 310 315 320 Pro Asp Ala Leu Leu Val Pro Val Ala Val Thr Tyr Asp Leu Val Pro 325 330 335 Asp Ala Pro Cys Asp Ile Asp His Ala Ser Ala Pro Leu Gly Leu Trp 340 345 350 Thr Gly Ala Leu Ala Val Leu Arg Ser Leu Trp Ser Arg Trp Gly Cys 355 360 365 Ser His Arg Ile Cys Ser Arg Val His Leu Ala Gln Pro Phe Ser Leu 370 375 380 Gln Glu Tyr Ile Val Ser Ala Arg Ser Cys Trp Gly Gly Arg Gln Thr 385 390 395 400 Leu Glu Gln Leu Leu Gln Pro Ile Val Leu Gly Gln Cys Thr Ala Val 405 410 415 Pro Asp Thr Glu Lys Glu Gln Glu Trp Thr Pro Ile Thr Gly Pro Leu 420 425 430 Leu Ala Leu Lys Glu Glu Asp Gln Leu Leu Val Arg Arg Leu Ser Cys 435 440 445 His Val Leu Ser Ala Ser Val Gly Ser Ser Ala Val Met Ser Thr Ala 450 455 460 Ile Met Ala Thr Leu Leu Leu Phe Lys His Gln Lys Gly Val Phe Leu 465 470 475 480 Ser Gln Leu Leu Gly Glu Phe Ser Trp Leu Thr Glu Glu Ile Leu Leu 485 490 495 Arg Gly Phe Asp Val Gly Phe Ser Gly Gln Leu Arg Ser Leu Leu Gln 500 505 510 His Ser Leu Ser Leu Leu Arg Ala His Val Ala Leu Leu Arg Ile Arg 515 520 525 Gln Gly Asp Leu Leu Val Val Pro Gln Pro Gly Pro Gly Leu Thr His 530 535 540 Leu Ala Gln Leu Ser Ala Glu Leu Leu Pro Val Phe Leu Ser Glu Ala 545 550 555 560 Val Gly Ala Cys Ala Val Arg Gly Leu Leu Ala Gly Arg Val Pro Pro 565 570 575 Gln Gly Pro Trp Glu Leu Gln Gly Ile Leu Leu Leu Ser Gln Asn Glu 580 585 590 Leu Tyr Arg Gln Ile Leu Leu Leu Met His Leu Leu Pro Gln Asp Leu 595 600 605 Leu Leu Leu Lys Thr Pro Gly Ser Arg Pro Ala Cys Asp Thr Gly Arg 610 615 620 Gln Arg Leu Ser Arg Lys Leu Leu Trp Lys Pro Ser Gly Asp Phe Thr 625 630 635 640 Asp Ser Asp Ser Asp Asp Phe Gly Glu Ala Asp Gly Arg Tyr Phe Arg 645 650 655 Leu Ser Gln Gln Ser His Cys Pro Asp Phe Phe Leu Phe Leu Cys Arg 660 665 670 Leu Leu Ser Pro Leu Leu Lys Ala Phe Ala Gln Ala Ala Ala Phe Leu 675 680 685 Arg Gln Gly Gln Leu Pro Asp Thr Glu Leu Gly Tyr Thr Glu Gln Leu 690 695 700 Phe Gln Phe Leu Gln Ala Thr Ala Gln Glu Glu Gly Ile Phe Glu Cys 705 710 715 720 Ala Asp Pro Lys Leu Ala Ile Ser Ala Val Trp Thr Phe Arg Asp Leu 725 730 735 Gly Val Leu Gln Gln Thr Pro Ser Pro Ala Gly Pro Arg Leu His Leu 740 745 750 Ser Pro Thr Phe Ala Ser Leu Asp Asn Gln Glu Lys Leu Glu Gln Phe 755 760 765 Ile Arg Gln Phe Ile Cys Ser 770 775 33 2604 DNA Homo Sapiens 33 atgaacatac atcacaatgt gaacagtggt catctccaga tagtagaatt tcagatatgt 60 ttctttccat ttttctgaca gtttgaattt tctgtaataa ttaattgact tttatacaat 120 ggaaacaact tttttgtttt ggaaaaagaa agatgctgcc gctaatcagt ggatgaaaga 180 tgataatatg gatacaaaat ctattctaga agaacttctt ctcaaaagat cacagcaaaa 240 gaagaaaatg tcaccaaata attacaaaga acggcttttt gttttgacca aaacaaacct 300 ttcctactat gaatatgaca aaatgaaaag gggcagcaga aaaggatcca ttgaaattaa 360 gaaaatcaga tgtgtggaga aagtaaatct cgaggagcag acgcctgtag agagacagta 420 cccatttcag attgtctata aagatgggct tctctatgtc tatgcatcaa atgaagagag 480 ccgaagtcag tggttgaaag cattacaaaa agagataagg ggtaaccccc acctgctggt 540 caagtaccat agtgggttct tcgtggacgg gaagttcctg tgttgccagc agagctgtaa 600 agcagcccca ggatgtaccc tctgggaagc atatgctaat ctgcatactg cagtcaatga 660 agagaaacac agagttccca ccttcccaga cagagtgctg aagatacctc gggcagttcc 720 tgttctcaaa atggatgcac catcttcaag taccactcta gcccaatatg acaacgaatc 780 aaagaaaaac tatggctccc agccaccatc ttcaagtacc agtctagcgc aatatgacag 840 caactcaaag aaaatctatg gctcccagcc aaacttcaac atgcagtata ttccaaggga 900 agacttccct gactggtggc aagtaagaaa actgaaaagt agcagcagca gtgaagatgt 960 tgcaagcagt aaccaaaaag aaagaaatgt gaatcacacc acctcaaaga tttcatggga 1020 attccctgag tcaagttcat ctgaagaaga ggaaaacctg gatgattatg actggtttgc 1080 tggtaacatc tccagatcac aatctgaaca gttactcaga caaaagggaa aagaaggagc 1140 atttatggtt agaaattcga gccaagtggg aatgtacaca gtgtccttat ttagtaaggc 1200 tgtgaatgat aaaaaaggaa ctgtcaaaca ttaccacgtg catacaaatg ctgagaacaa 1260 attatacctg gcagaaaact actgttttga ttccattcca aagcttattc attatcatca 1320 acacaattca gcaggcatga tcacacgccg ccaccctgtg tcaacaaagg ccaacaaggt 1380 ccccgactct gtgtccctgg caaatggaat ctgggaactg aaaagagaag agattacctt 1440 gttgaaggag ctgggaagtg gccagtttgg agtggtccag ctgggcaagt ggaaggggca 1500 gtatgatgtt gctgttaaga tgatcaagga gggctccatg tcagaagatg aattctttca 1560 ggaggcccag actatgatga aactcagcca tcccaagctg gttaaattct atggagtgtg 1620 ttcaaaggaa taccccatat acatagtgac tgaatatata agcaatggct gcttgctgaa 1680 ttacctgagg agtcacggaa aaggacttga accttcccag ctcttagaaa tgtgctacga 1740 tgtctgtgaa ggcatggcct tcttggagag tcaccaattc atacaccggg acttggctgc 1800 tcgtaactgc ttggtggaca gagatctctg tgtgaaagta tctgactttg gaatgacaag 1860 gtatgttctt gatgaccagt atgtcagttc agtcggaaca aagtttccag tcaagtggtc 1920 agctccagag gtgtttcatt acttcaaata cagcagcaag tcagacgtat gggcatttgg 1980 gatcctgatg tgggaggtgt tcagcctggg gaagcagccc tatgacttgt atgacaactc 2040 ccaggtggtt ctgaaggtct cccagggcca caggctttac cggccccacc tggcatcgga 2100 caccatctac cagatcatgt acagctgctg gcacgagctt ccagaaaagc gtcccacatt 2160 tcagcaactc ctgtcttcca ttgaaccact tcgggaaaaa gacaagcatt gaagaagaaa 2220 ttaggagtgc tgataagaat gaatatagat gctggccagc attttcattc attttaagga 2280 aagtagcaag gcataatgta atttagctag tttttaatag tgttctctgt attgtctatt 2340 atttagaaat gaacaaggca ggaaacaaaa gattcccttg aaatttagat caaattagta 2400 attttgtttt atgctgctcc tgatataaca ctttccagcc tatagcagaa gcacattttc 2460 agactgcaat atagagactg tgttcatgtg taaagactga gcagaactga aaaattactt 2520 attggatatt cattcttttc tttatattgt cattgtcaca acaattaaat atactaccaa 2580 gtacagaaat gtggaaaaaa aaaa 2604 34 697 PRT Homo Sapiens 34 Met Glu Thr Thr Phe Leu Phe Trp Lys Lys Lys Asp Ala Ala Ala Asn 1 5 10 15 Gln Trp Met Lys Asp Asp Asn Met Asp Thr Lys Ser Ile Leu Glu Glu 20 25 30 Leu Leu Leu Lys Arg Ser Gln Gln Lys Lys Lys Met Ser Pro Asn Asn 35 40 45 Tyr Lys Glu Arg Leu Phe Val Leu Thr Lys Thr Asn Leu Ser Tyr Tyr 50 55 60 Glu Tyr Asp Lys Met Lys Arg Gly Ser Arg Lys Gly Ser Ile Glu Ile 65 70 75 80 Lys Lys Ile Arg Cys Val Glu Lys Val Asn Leu Glu Glu Gln Thr Pro 85 90 95 Val Glu Arg Gln Tyr Pro Phe Gln Ile Val Tyr Lys Asp Gly Leu Leu 100 105 110 Tyr Val Tyr Ala Ser Asn Glu Glu Ser Arg Ser Gln Trp Leu Lys Ala 115 120 125 Leu Gln Lys Glu Ile Arg Gly Asn Pro His Leu Leu Val Lys Tyr His 130 135 140 Ser Gly Phe Phe Val Asp Gly Lys Phe Leu Cys Cys Gln Gln Ser Cys 145 150 155 160 Lys Ala Ala Pro Gly Cys Thr Leu Trp Glu Ala Tyr Ala Asn Leu His 165 170 175 Thr Ala Val Asn Glu Glu Lys His Arg Val Pro Thr Phe Pro Asp Arg 180 185 190 Val Leu Lys Ile Pro Arg Ala Val Pro Val Leu Lys Met Asp Ala Pro 195 200 205 Ser Ser Ser Thr Thr Leu Ala Gln Tyr Asp Asn Glu Ser Lys Lys Asn 210 215 220 Tyr Gly Ser Gln Pro Pro Ser Ser Ser Thr Ser Leu Ala Gln Tyr Asp 225 230 235 240 Ser Asn Ser Lys Lys Ile Tyr Gly Ser Gln Pro Asn Phe Asn Met Gln 245 250 255 Tyr Ile Pro Arg Glu Asp Phe Pro Asp Trp Trp Gln Val Arg Lys Leu 260 265 270 Lys Ser Ser Ser Ser Ser Glu Asp Val Ala Ser Ser Asn Gln Lys Glu 275 280 285 Arg Asn Val Asn His Thr Thr Ser Lys Ile Ser Trp Glu Phe Pro Glu 290 295 300 Ser Ser Ser Ser Glu Glu Glu Glu Asn Leu Asp Asp Tyr Asp Trp Phe 305 310 315 320 Ala Gly Asn Ile Ser Arg Ser Gln Ser Glu Gln Leu Leu Arg Gln Lys 325 330 335 Gly Lys Glu Gly Ala Phe Met Val Arg Asn Ser Ser Gln Val Gly Met 340 345 350 Tyr Thr Val Ser Leu Phe Ser Lys Ala Val Asn Asp Lys Lys Gly Thr 355 360 365 Val Lys His Tyr His Val His Thr Asn Ala Glu Asn Lys Leu Tyr Leu 370 375 380 Ala Glu Asn Tyr Cys Phe Asp Ser Ile Pro Lys Leu Ile His Tyr His 385 390 395 400 Gln His Asn Ser Ala Gly Met Ile Thr Arg Arg His Pro Val Ser Thr 405 410 415 Lys Ala Asn Lys Val Pro Asp Ser Val Ser Leu Ala Asn Gly Ile Trp 420 425 430 Glu Leu Lys Arg Glu Glu Ile Thr Leu Leu Lys Glu Leu Gly Ser Gly 435 440 445 Gln Phe Gly Val Val Gln Leu Gly Lys Trp Lys Gly Gln Tyr Asp Val 450 455 460 Ala Val Lys Met Ile Lys Glu Gly Ser Met Ser Glu Asp Glu Phe Phe 465 470 475 480 Gln Glu Ala Gln Thr Met Met Lys Leu Ser His Pro Lys Leu Val Lys 485 490 495 Phe Tyr Gly Val Cys Ser Lys Glu Tyr Pro Ile Tyr Ile Val Thr Glu 500 505 510 Tyr Ile Ser Asn Gly Cys Leu Leu Asn Tyr Leu Arg Ser His Gly Lys 515 520 525 Gly Leu Glu Pro Ser Gln Leu Leu Glu Met Cys Tyr Asp Val Cys Glu 530 535 540 Gly Met Ala Phe Leu Glu Ser His Gln Phe Ile His Arg Asp Leu Ala 545 550 555 560 Ala Arg Asn Cys Leu Val Asp Arg Asp Leu Cys Val Lys Val Ser Asp 565 570 575 Phe Gly Met Thr Arg Tyr Val Leu Asp Asp Gln Tyr Val Ser Ser Val 580 585 590 Gly Thr Lys Phe Pro Val Lys Trp Ser Ala Pro Glu Val Phe His Tyr 595 600 605 Phe Lys Tyr Ser Ser Lys Ser Asp Val Trp Ala Phe Gly Ile Leu Met 610 615 620 Trp Glu Val Phe Ser Leu Gly Lys Gln Pro Tyr Asp Leu Tyr Asp Asn 625 630 635 640 Ser Gln Val Val Leu Lys Val Ser Gln Gly His Arg Leu Tyr Arg Pro 645 650 655 His Leu Ala Ser Asp Thr Ile Tyr Gln Ile Met Tyr Ser Cys Trp His 660 665 670 Glu Leu Pro Glu Lys Arg Pro Thr Phe Gln Gln Leu Leu Ser Ser Ile 675 680 685 Glu Pro Leu Arg Glu Lys Asp Lys His 690 695 35 6629 DNA Homo Sapiens 35 tggaatttga tccggaagaa ttttactacc tattggaagc agcagaaggc catgccaaag 60 aaggacaggg tattaaaacc gacattccca ggtacatcat tagccaactg ggactcaata 120 aggatccctt ggaagaaatg gctcatttgg gaaactacga tagtgggaca gcagaaacac 180 cagaaacaga tgaatcagtg agtagctcta atgcctccct gaaacttcga aggaaacctc 240 gggaaagtga ttttgaaacg attaaattga ttagcaatgg agcctatggg gcagtctact 300 ttgttcggca taaagaatcc cggcagaggt ttgccatgaa gaagattaat aaacagaacc 360 tcatccttcg aaaccagatc cagcaggcct ttgtggagcg ggatatcctg acttttgcag 420 aaaacccctt tgttgtcagc atgtattgct cctttgaaac aaggcgccac ttgtgcatgg 480 tcatggaata tgtggaaggg ggagactgtg ctactttaat gaaaaacatg ggtcctctcc 540 ctgttgatat ggccagaatg tactttgctg agacggtctt ggccttggaa tatttacata 600 attatggaat tgtacacagg gatttgaaac cagacaactt gttggttacc tccatggggc 660 acataaagct gacagatttt ggattatcta aggtgggact aatgagcatg actaccaacc 720 tttacgaggg tcatattgag aaggatgcta gagagttcct ggataaacag gtctgtggca 780 cacctgaata cattgcacca gaagtgattc tgaggcaggg ttatggaaag ccggtggact 840 ggtgggccat ggggattatc ctctatgaat ttctggttgg atgcgtgcca ttctttgggg 900 atactccaga ggagctattt ggacaagtca tcagtgatga gatcaactgg cctgagaagg 960 atgaggcacc cccacctgat gcccaggatc tgattacctt actcctcagg cagaatcccc 1020 tggagaggct gggaacaggt ggtgcatatg aagtcaaaca gcatcgattc ttccgttctt 1080 tagactggaa cagtttgctg agacagaagg cagaatttat tccccaactg gaatctgagg 1140 atgacacaag ttattttgat actcggtctg agaagtatca tcatatggaa acggaggaag 1200 aagatgacac aaatgatgaa gactttaatg tggaaataag gcagttttct tcatgttcac 1260 acaggttttc aaaagttttc agcagtatag atcgaatcac tcagaattca gcagaagaga 1320 aggaagactc tgtggacaaa accaaaagca ccaccttgcc atccacagaa acactgagct 1380 ggagttcaga atattctgaa atgcaacagc tatcaacatc caactcttca gatactgaaa 1440 gcaacagaca taaactcagt tctggcctac ttcccaaact ggctatttca acagagggag 1500 agcaagatga agctgcctcc tgccctggag acccccatga ggagccagga aagccagccc 1560 ttcctcctga agagtgtgcc caggaggagc ctgaggtcac caccccagcc agcaccatca 1620 gcagctccac cctgtcagtt ggcagttttt cagagcactt ggatcagata aatggacgaa 1680 gcgagtgtgt ggacagtaca gataattcct caaagccatc cagtgaaccc gcttctcaca 1740 tggctcggca gcgattagaa agcacagaaa aaaagaaaat ctcggggaaa gtcacaaagt 1800 ccctctctgc cagtgctctt tccctcatga tcccaggaga tatgtttgct gtttcccctc 1860 tgggaagtcc aatgtctccc cattccctgt cctcggaccc ttcttcttca cgagattcct 1920 ctcccagccg agattcctca gcagcttctg ccagtccaca tcagccgatt gtgatccaca 1980 gttcggggaa gaactacggc tttaccatcc gagccatccg ggtgtatgtg ggagacagtg 2040 acatctatac agtgcaccat atcgtctgga atgtagaaga aggaagtccg gcatgccagg 2100 caggactgaa ggctggagat cttatcactc acatcaatgg agaaccagtg catggacttg 2160 tccacacaga agttatagaa ctcctactga agagtgggaa taaggtgtca atcactacta 2220 ccccatttga aaacacatca atcaaaactg gaccagccag gagaaacagc tataagagcc 2280 ggatggtgag gcggagcaag aaatccaaga agaaagaaag tctcgaaagg aggagatctc 2340 ttttcaaaaa gctagccaag cagccttctc ctttactcca caccagccga agtttctcct 2400 gcttgaacag atccctgtca tcgggtgaga gcctcccagg ttcccccact catagcttgt 2460 ctccccggtc tccaacacca agctaccgct ccacccctga cttcccatct ggtactaatt 2520 cctcccagag cagctcccct agttctagtg cccccaattc cccagcaggg tccgggcaca 2580 tccggcccag cactctccac ggtcttgcac ccaaactcgg cgggcagcgg taccggtccg 2640 gaaggcgaaa gtccgccggc aacatcccac tgtccccgct ggcccggacg ccctctccaa 2700 ccccgcaacc cacctccccg cagcggtcac catcccctct tctgggacac tcactgggca 2760 attccaagat cgcgcaagcc tttcccagca agatgcactc cccgcccacc atcgtcagac 2820 acatcgtgag gcccaagagt gcggagcccc ccaggtcccc gctgctcaag cgcgtgcagt 2880 ccgaggagaa gctgtcgccc tcttacggca gtgacaagaa gcacctgtgc tcccgcaagc 2940 acagcctgga ggtgacccaa gaggaggtgc agcgggagca gtcccagcgg gaggcgccgc 3000 tgcagagcct ggatgagaac gtgtgcgacg tgccgccgct cagccgcgcc cggccagtgg 3060 agcaaggctg cctgaaacgc ccagtctccc ggaaggtggg ccgccaggag tctgtggacg 3120 acctggaccg cgacaagctg aaggccaagg tggtggtgaa gaaagcagac ggcttcccag 3180 agaaacagga atcccaccag aaatcccatg gacccgggag tgatttggaa aactttgctc 3240 tgtttaagct ggaagagaga gagaagaaag tctatccgaa ggctgtggaa aggtcaagta 3300 cttttgaaaa caaagcgtct atgcaggagg cgccaccgct gggcagcctg ctgaaggatg 3360 ctcttcacaa gcaggccagc gtgcgcgcca gcgagggtgc gatgtcggat ggcccggtgc 3420 ctgcggagca ccgccagggt ggcggggact tcagacgggc ccccgctcct ggcaccctcc 3480 aggatggtct ctgccactcc ctcgacaggg gcatctctgg gaagggggaa ggcacggaga 3540 agtcctccca ggccaaggag cttctccgat gtgaaaagtt agacagcaag ctggccaaca 3600 tcgattacct ccgaaagaaa atgtcacttg aggacaaaga ggacaacctc tgccctgtgc 3660 tgaagcccaa gatgacagct ggctcccacg aatgcctgcc agggaaccca gtccgaccca 3720 cgggtgggca gcaggagccc ccgccggctt ctgagagccg agcttttgtc agcagcaccc 3780 atgcagctca gatgagtgcc gtctcttttg ttcccctcaa ggccttaaca ggccgggtgg 3840 acagtggaac ggagaagcct ggcttggttg ctcctgagtc ccctgttagg aagagcccct 3900 ccgagtataa gctggaaggt aggtctgtct catgcctgga gccgatcgag ggcactctgg 3960 acattgctct cctgtccgga cctcaggcct ccaagacaga actgccttcc ccagagtctg 4020 cacagagccc cagcccaagt ggtgacgtga gggcctctgt gccaccagtt ctccccagca 4080 gcagtgggaa aaagaacgat accaccagtg caagagagct ttctccttcc agcttaaaga 4140 tgaataaatc ctacctgctg gagccttggt tcctgccccc cagccgaggt ctccagaatt 4200 caccagcagt ttccctgcct gacccagagt tcaagaggga caggaaaggt ccccatccta 4260 ctgccaggag ccctggaaca gtcatggaaa gcaatcccca acagagagag ggcagctccc 4320 ctaaacacca agaccacacc actgacccca agcttctgac ctgcctgggg cagaacctcc 4380 acagccctga cctggccagg ccacgctgcc cgctcccacc tgaagcttcc ccctcaaggg 4440 agaagccagg cctgagggaa tcgtctgaaa gaggccctcc cacagccaga agcgagcgct 4500 ctgctgcgag ggctgacaca tgcagagagc cctccatgga actgtgcttt ccagaaactg 4560 cgaaaaccag tgacaactcc aaaaatctcc tctctgtggg aaggacccac ccagatttct 4620 atacacagac ccaggccatg gagaaagcat gggcgccggg tgggaaaacg aaccacaaag 4680 atggcccagg tgaggcgagg cccccgccca gagacaactc ctctctgcac tcagctggaa 4740 ttccctgtga gaaggagctg ggcaaggtga ggcgtggcgt ggaacccaag cccgaagcgc 4800 ttcttgccag gcggtctctg cagccacctg gaattgagag tgagaagagt gaaaagctct 4860 ccagtttccc atctttgcag aaagatggtg ccaaggaacc tgaaaggaag gagcagcctc 4920 tacaaaggca tcccagcagc atccctccgc cccctctgac ggccaaagac ctgtccagcc 4980 cggctgccag gcagcattgc agttccccaa gccacgcttc tggcagagag ccgggggcca 5040 agcccagcac tgcagagccc agctcgagcc cccaggaccc tcccaagcct gttgctgcgc 5100 acagtgaaag cagcagccac aagccccggc ctggccctga cccgggccct ccaaagacta 5160 agcaccccga ccggtccctc tcctctcaga aaccaagtgt cggggccaca aagggcaaag 5220 agcctgccac tcagtccctc ggtggctcta gcagagaggg gaagggccac agtaagagtg 5280 ggccggatgt gtttcctgct accccaggct cccagaacaa agccagcgat gggattggcc 5340 agggagaagg tgggccctct gtcccactgc acactgacag ggctcctcta gacgccaagc 5400 cacaacccac cagtggtggg cggcccctgg aggtgctgga gaagcctgtg catttgccaa 5460 ggccgggaca cccagggcct agtgagccag cggaccagaa actgtccgct gttggtgaaa 5520 agcaaaccct gtctccaaag caccccaaac catccactgt gaaagattgc cccaccctgt 5580 gcaaacagac agacaacaga cagacagaca aaagcccgag tcagccggcc gccaacaccg 5640 acagaagggc ggaagggaag aaatgcactg aagcacttta tgctccagca gagggcgaca 5700 agctcgaggc cggcctttcc tttgtgcata gcgagaaccg gttgaaaggc gcggagcggc 5760 cagccgcggg ggtggggaag ggcttccctg aggccagagg gaaagggccc ggtccccaga 5820 agccaccgac ggaggcagac aagcccaatg gcatgaaacg gtccccctca gccactgggc 5880 agagttcttt ccgatccacg gccctcccgg aaaagtctct gagctgctcc tccagcttcc 5940 ctgaaaccag ggccggagtt agagaggcct ctgcagccag cagcgacacc tcttctgcca 6000 aggccgccgg gggcatgctg gagcttccag cccccagcaa cagggaccat aggaaggctc 6060 agcctgccgg ggagggccga acccacatga caaagagtga ctccctgccc tccttccggg 6120 tctccaccct gcctctggag tcacaccacc ccgacccaaa caccatgggc ggggccagcc 6180 accgggacag ggctctctcg gtgactgcca ccgtagggga aaccaaaggg aaggaccctg 6240 ccccagccca gcctccccca gctaggaaac agaacgtggg cagagacgtg accaagccat 6300 ccccagcccc aaacactgac cgccccatct ctctttctaa tgagaaggac tttgtggtac 6360 ggcagaggcg ggggaaagag agtttgcgta gcagccctca caaaaaggcc ttgtaacggg 6420 gagggcccag gggcaggact gtggagaccc gtcctgaacg ggcgactgtg tcttgactac 6480 ctttcaaaac cagcactgtg tgggaatgtc cgccaggcag agctcggagc ctcattgaga 6540 caggggagag agaaagacaa agaggggacc ttcttccaga tgccttccca gttgtaaccg 6600 gtaaaactgt taccagatag tgtttgtac 6629 36 2080 PRT Homo Sapiens VARIANT (1)...(2080) Xaa = Any Amino Acid 36 Trp Asn Leu Ile Arg Lys Asn Phe Thr Thr Tyr Trp Lys Gln Gln Lys 1 5 10 15 Ala Met Pro Lys Lys Asp Arg Val Leu Lys Pro Thr Phe Pro Gly Thr 20 25 30 Ser Leu Ala Asn Trp Asp Ser Ile Arg Ile Pro Trp Lys Lys Trp Leu 35 40 45 Ile Trp Glu Thr Thr Ile Val Gly Gln Gln Lys His Gln Lys Gln Met 50 55 60 Asn Gln Val Ala Leu Met Pro Pro Asn Phe Glu Gly Asn Leu Gly Lys 65 70 75 80 Val Ile Leu Lys Arg Leu Asn Leu Ala Met Glu Pro Met Gly Gln Ser 85 90 95 Thr Leu Phe Gly Ile Lys Asn Pro Gly Arg Gly Leu Pro Arg Arg Leu 100 105 110 Ile Asn Arg Thr Ser Ser Phe Glu Thr Arg Ser Ser Arg Pro Leu Trp 115 120 125 Ser Gly Ile Ser Leu Leu Gln Lys Thr Pro Leu Leu Ser Ala Cys Ile 130 135 140 Ala Pro Leu Lys Gln Gly Ala Thr Cys Ala Trp Ser Trp Asn Met Trp 145 150 155 160 Lys Gly Glu Thr Val Leu Leu Lys Thr Trp Val Leu Ser Leu Leu Ile 165 170 175 Trp Pro Glu Cys Thr Leu Leu Arg Arg Ser Trp Pro Trp Asn Ile Tyr 180 185 190 Ile Ile Met Glu Leu Tyr Thr Gly Ile Asn Gln Thr Thr Cys Trp Leu 195 200 205 Pro Pro Trp Gly Thr Ser Gln Ile Leu Asp Tyr Leu Arg Trp Asp Ala 210 215 220 Leu Pro Thr Phe Thr Arg Val Ile Leu Arg Arg Met Leu Glu Ser Ser 225 230 235 240 Trp Ile Asn Arg Ser Val Ala His Leu Asn Thr Leu His Gln Lys Phe 245 250 255 Gly Arg Val Met Glu Ser Arg Trp Thr Gly Gly Pro Trp Gly Leu Ser 260 265 270 Ser Met Asn Phe Trp Leu Asp Ala Cys His Ser Leu Gly Ile Leu Gln 275 280 285 Arg Ser Tyr Leu Asp Lys Ser Ser Val Met Arg Ser Thr Gly Leu Arg 290 295 300 Arg Met Arg His Pro His Leu Met Pro Arg Ile Leu Pro Tyr Ser Ser 305 310 315 320 Gly Arg Ile Pro Trp Arg Gly Trp Glu Gln Val Val His Met Lys Ser 325 330 335 Asn Ser Ile Asp Ser Ser Val Leu Thr Gly Thr Val Cys Asp Arg Arg 340 345 350 Gln Asn Leu Phe Pro Asn Trp Asn Leu Arg Met Thr Gln Val Ile Leu 355 360 365 Ile Leu Gly Leu Arg Ser Ile Ile Ile Trp Lys Arg Arg Lys Lys Met 370 375 380 Thr Gln Met Met Lys Thr Leu Met Trp Lys Gly Ser Phe Leu His Val 385 390 395 400 His Thr Gly Phe Gln Lys Phe Ser Ala Val Ile Glu Ser Leu Arg Ile 405 410 415 Gln Gln Lys Arg Arg Lys Thr Leu Trp Thr Lys Pro Lys Ala Pro Pro 420 425 430 Cys His Pro Gln Lys His Ala Gly Val Gln Asn Ile Leu Lys Cys Asn 435 440 445 Ser Tyr Gln His Pro Thr Leu Gln Ile Leu Lys Ala Thr Asp Ile Asn 450 455 460 Ser Val Leu Ala Tyr Phe Pro Asn Trp Leu Phe Gln Gln Arg Glu Ser 465 470 475 480 Lys Met Lys Leu Pro Pro Ala Leu Glu Thr Pro Met Arg Ser Gln Glu 485 490 495 Ser Gln Pro Phe Leu Leu Lys Ser Val Pro Arg Arg Ser Leu Arg Ser 500 505 510 Pro Pro Gln Pro Ala Pro Ser Ala Ala Pro Pro Cys Gln Leu Ala Val 515 520 525 Phe Gln Ser Thr Trp Ile Arg Met Asp Glu Ala Ser Val Trp Thr Val 530 535 540 Gln Ile Ile Pro Gln Ser His Pro Val Asn Pro Leu Leu Thr Trp Leu 545 550 555 560 Gly Ser Asp Lys Ala Gln Lys Lys Arg Lys Ser Arg Gly Lys Ser Gln 565 570 575 Ser Pro Ser Leu Pro Val Leu Phe Pro Ser Ser Gln Glu Ile Cys Leu 580 585 590 Leu Phe Pro Leu Trp Glu Val Gln Cys Leu Pro Ile Pro Cys Pro Arg 595 600 605 Thr Leu Leu Leu His Glu Ile Pro Leu Pro Ala Glu Ile Pro Gln Gln 610 615 620 Leu Leu Pro Val His Ile Ser Arg Leu Ser Thr Val Arg Gly Arg Thr 625 630 635 640 Thr Ala Leu Pro Ser Glu Pro Ser Gly Cys Met Trp Glu Thr Val Thr 645 650 655 Ser Ile Gln Cys Thr Ile Ser Ser Gly Met Lys Lys Glu Val Arg His 660 665 670 Ala Arg Gln Asp Arg Leu Glu Ile Leu Ser Leu Thr Ser Met Glu Asn 675 680 685 Gln Cys Met Asp Leu Ser Thr Gln Lys Leu Asn Ser Tyr Arg Val Gly 690 695 700 Ile Arg Cys Gln Ser Leu Leu Pro His Leu Lys Thr His Gln Ser Lys 705 710 715 720 Leu Asp Gln Pro Gly Glu Thr Ala Ile Arg Ala Gly Trp Gly Gly Ala 725 730 735 Arg Asn Pro Arg Arg Lys Lys Val Ser Lys Gly Gly Asp Leu Phe Ser 740 745 750 Lys Ser Pro Ser Ser Leu Leu Leu Tyr Ser Thr Pro Ala Glu Val Ser 755 760 765 Pro Ala Thr Asp Pro Cys His Arg Val Arg Ala Ser Gln Val Pro Pro 770 775 780 Leu Ile Ala Cys Leu Pro Gly Leu Gln His Gln Ala Thr Ala Pro Pro 785 790 795 800 Leu Thr Ser His Leu Val Leu Ile Pro Pro Arg Ala Ala Pro Leu Val 805 810 815 Leu Val Pro Pro Ile Pro Gln Gln Gly Pro Gly Thr Ser Gly Pro Ala 820 825 830 Leu Ser Thr Val Leu His Pro Asn Ser Ala Gly Ser Gly Thr Gly Pro 835 840 845 Glu Gly Glu Ser Pro Pro Ala Thr Ser His Cys Pro Arg Trp Pro Gly 850 855 860 Arg Pro Leu Gln Pro Arg Asn Pro Pro Pro Arg Ser Gly His His Pro 865 870 875 880 Leu Phe Trp Asp Thr His Trp Ala Ile Pro Arg Ser Arg Lys Pro Phe 885 890 895 Pro Ala Arg Cys Thr Pro Arg Pro Pro Ser Ser Asp Thr Ser Gly Pro 900 905 910 Arg Val Arg Ser Pro Pro Gly Pro Arg Cys Ser Ser Ala Cys Ser Pro 915 920 925 Arg Arg Ser Cys Arg Pro Leu Thr Ala Val Thr Arg Ser Thr Cys Ala 930 935 940 Pro Ala Ser Thr Ala Trp Arg Pro Lys Arg Arg Cys Ser Gly Ser Ser 945 950 955 960 Pro Ser Gly Arg Arg Arg Cys Arg Ala Trp Met Arg Thr Cys Ala Thr 965 970 975 Cys Arg Arg Ser Ala Ala Pro Gly Gln Trp Ser Lys Ala Ala Asn Ala 980 985 990 Gln Ser Pro Gly Arg Trp Ala Ala Arg Ser Leu Trp Thr Thr Trp Thr 995 1000 1005 Ala Thr Ser Arg Pro Arg Trp Trp Arg Lys Gln Thr Ala Ser Gln Arg 1010 1015 1020 Asn Arg Asn Pro Thr Arg Asn Pro Met Asp Pro Gly Val Ile Trp Lys 1025 1030 1035 1040 Thr Leu Leu Cys Leu Ser Trp Lys Arg Glu Arg Arg Lys Ser Ile Arg 1045 1050 1055 Arg Leu Trp Lys Gly Gln Val Leu Leu Lys Thr Lys Arg Leu Cys Arg 1060 1065 1070 Arg Arg His Arg Trp Ala Ala Cys Arg Met Leu Phe Thr Ser Arg Pro 1075 1080 1085 Ala Cys Ala Pro Ala Arg Val Arg Cys Arg Met Ala Arg Cys Leu Arg 1090 1095 1100 Ser Thr Ala Arg Val Ala Gly Thr Ser Asp Gly Pro Pro Leu Leu Ala 1105 1110 1115 1120 Pro Ser Arg Met Val Ser Ala Thr Pro Ser Thr Gly Ala Ser Leu Gly 1125 1130 1135 Arg Gly Lys Ala Arg Arg Ser Pro Pro Arg Pro Arg Ser Phe Ser Asp 1140 1145 1150 Val Lys Ser Thr Ala Ser Trp Pro Thr Ser Ile Thr Ser Glu Arg Lys 1155 1160 1165 Cys His Leu Arg Thr Lys Arg Thr Thr Ser Ala Leu Cys Ser Pro Arg 1170 1175 1180 Gln Leu Ala Pro Thr Asn Ala Cys Gln Gly Thr Gln Ser Asp Pro Arg 1185 1190 1195 1200 Val Gly Ser Arg Ser Pro Arg Arg Leu Leu Arg Ala Glu Leu Leu Ser 1205 1210 1215 Ala Ala Pro Met Gln Leu Arg Val Pro Ser Leu Leu Phe Pro Ser Arg 1220 1225 1230 Pro Gln Ala Gly Trp Thr Val Glu Arg Arg Ser Leu Ala Trp Leu Leu 1235 1240 1245 Leu Ser Pro Leu Leu Gly Arg Ala Pro Pro Ser Ile Ser Trp Lys Val 1250 1255 1260 Gly Leu Ser His Ala Trp Ser Arg Ser Arg Ala Leu Trp Thr Leu Leu 1265 1270 1275 1280 Ser Cys Pro Asp Leu Arg Pro Pro Arg Gln Asn Cys Leu Pro Gln Ser 1285 1290 1295 Leu His Arg Ala Pro Ala Gln Val Val Thr Gly Pro Leu Cys His Gln 1300 1305 1310 Phe Ser Pro Ala Ala Val Gly Lys Arg Thr Ile Pro Pro Val Gln Glu 1315 1320 1325 Ser Phe Leu Leu Pro Ala Arg Ile Asn Pro Thr Cys Trp Ser Leu Gly 1330 1335 1340 Ser Cys Pro Pro Ala Glu Val Ser Arg Ile His Gln Gln Phe Pro Cys 1345 1350 1355 1360 Leu Thr Gln Ser Ser Arg Gly Thr Gly Lys Val Pro Ile Leu Leu Pro 1365 1370 1375 Gly Ala Leu Glu Gln Ser Trp Lys Ala Ile Pro Asn Arg Glu Arg Ala 1380 1385 1390 Ala Pro Leu Asn Thr Lys Thr Thr Pro Leu Thr Pro Ser Phe Pro Ala 1395 1400 1405 Trp Gly Arg Thr Ser Thr Ala Leu Thr Trp Pro Gly His Ala Ala Arg 1410 1415 1420 Ser His Leu Lys Leu Pro Pro Gln Gly Arg Ser Gln Ala Gly Asn Arg 1425 1430 1435 1440 Leu Lys Glu Ala Leu Pro Gln Pro Glu Ala Ser Ala Leu Leu Arg Gly 1445 1450 1455 Leu Thr His Ala Glu Ser Pro Pro Trp Asn Cys Ala Phe Gln Lys Leu 1460 1465 1470 Arg Lys Pro Val Thr Thr Pro Lys Ile Ser Ser Leu Trp Glu Gly Pro 1475 1480 1485 Thr Gln Ile Ser Ile His Arg Pro Arg Pro Trp Arg Lys His Gly Arg 1490 1495 1500 Arg Val Gly Lys Arg Thr Thr Lys Met Ala Gln Val Arg Arg Gly Pro 1505 1510 1515 1520 Arg Pro Glu Thr Thr Pro Leu Cys Thr Gln Leu Glu Phe Pro Val Arg 1525 1530 1535 Arg Ser Trp Ala Arg Gly Val Ala Trp Asn Pro Ser Pro Lys Arg Phe 1540 1545 1550 Leu Pro Gly Gly Leu Cys Ser His Leu Glu Leu Arg Val Arg Arg Val 1555 1560 1565 Lys Ser Ser Pro Val Ser His Leu Cys Arg Lys Met Val Pro Arg Asn 1570 1575 1580 Leu Lys Gly Arg Ser Ser Leu Tyr Lys Gly Ile Pro Ala Ala Ser Leu 1585 1590 1595 1600 Arg Pro Leu Arg Pro Lys Thr Cys Pro Ala Arg Leu Pro Gly Ser Ile 1605 1610 1615 Ala Val Pro Gln Ala Thr Leu Leu Ala Glu Ser Arg Gly Pro Ser Pro 1620 1625 1630 Ala Leu Gln Ser Pro Ala Arg Ala Pro Arg Thr Leu Pro Ser Leu Leu 1635 1640 1645 Leu Arg Thr Val Lys Ala Ala Ala Thr Ser Pro Gly Leu Ala Leu Thr 1650 1655 1660 Arg Ala Leu Gln Arg Leu Ser Thr Pro Thr Gly Pro Ser Pro Leu Arg 1665 1670 1675 1680 Asn Gln Val Ser Gly Pro Gln Arg Ala Lys Ser Leu Pro Leu Ser Pro 1685 1690 1695 Ser Val Ala Leu Ala Glu Arg Gly Arg Ala Thr Val Arg Val Gly Arg 1700 1705 1710 Met Cys Phe Leu Leu Pro Gln Ala Pro Arg Thr Lys Pro Ala Met Gly 1715 1720 1725 Leu Ala Arg Glu Lys Val Gly Pro Leu Ser His Cys Thr Leu Thr Gly 1730 1735 1740 Leu Leu Thr Pro Ser His Asn Pro Pro Val Val Gly Gly Pro Trp Arg 1745 1750 1755 1760 Cys Trp Arg Ser Leu Cys Ile Cys Gln Gly Arg Asp Thr Gln Gly Leu 1765 1770 1775 Val Ser Gln Arg Thr Arg Asn Cys Pro Leu Leu Val Lys Ser Lys Pro 1780 1785 1790 Cys Leu Gln Ser Thr Pro Asn His Pro Leu Lys Ile Ala Pro Pro Cys 1795 1800 1805 Ala Asn Arg Gln Thr Thr Asp Arg Gln Thr Lys Ala Arg Val Ser Arg 1810 1815 1820 Pro Pro Thr Pro Thr Glu Gly Arg Lys Gly Arg Asn Ala Leu Lys His 1825 1830 1835 1840 Phe Met Leu Gln Gln Arg Ala Thr Ser Ser Arg Pro Ala Phe Pro Leu 1845 1850 1855 Cys Ile Ala Arg Thr Gly Lys Ala Arg Ser Gly Gln Pro Arg Gly Trp 1860 1865 1870 Gly Arg Ala Ser Leu Arg Pro Glu Gly Lys Gly Pro Val Pro Arg Ser 1875 1880 1885 His Arg Arg Arg Gln Thr Ser Pro Met Ala Asn Gly Pro Pro Gln Pro 1890 1895 1900 Leu Gly Arg Val Leu Ser Asp Pro Arg Pro Ser Arg Lys Ser Leu Ala 1905 1910 1915 1920 Ala Pro Pro Ala Ser Leu Lys Pro Gly Pro Glu Leu Glu Arg Pro Leu 1925 1930 1935 Gln Pro Ala Ala Thr Pro Leu Leu Pro Arg Pro Pro Gly Ala Cys Trp 1940 1945 1950 Ser Phe Gln Pro Pro Ala Thr Gly Thr Ile Gly Arg Leu Ser Leu Pro 1955 1960 1965 Gly Arg Ala Glu Pro Thr Gln Arg Val Thr Pro Cys Pro Pro Ser Gly 1970 1975 1980 Ser Pro Pro Cys Leu Trp Ser His Thr Thr Pro Thr Gln Thr Pro Trp 1985 1990 1995 2000 Ala Gly Pro Ala Thr Gly Thr Gly Leu Ser Arg Leu Pro Pro Gly Lys 2005 2010 2015 Pro Lys Gly Arg Thr Leu Pro Gln Pro Ser Leu Pro Gln Leu Gly Asn 2020 2025 2030 Arg Thr Trp Ala Glu Thr Pro Ser His Pro Gln Pro Gln Thr Leu Thr 2035 2040 2045 Ala Pro Ser Leu Phe Leu Met Arg Arg Thr Leu Trp Tyr Gly Arg Gly 2050 2055 2060 Gly Gly Lys Arg Val Cys Val Ala Ala Leu Thr Lys Arg Pro Cys Xaa 2065 2070 2075 2080 37 1945 DNA Homo Sapiens 37 agccatctct tcccaaggca ggtggtgact tgagaactct gtgcctggtt tctgaggact 60 gtttcaccat gcagtggcta atgaggttcc ggaccctctg gggcatccac aaatccttcc 120 acaacatcca ccctgcccct tcacagctgc gctgccggtc tttatcagaa tttggagccc 180 caagatggaa tgactatgaa gtaccggagg aatttaactt tgcaagttat gtactggact 240 actgggctca aaaggagaag gagggcaaga gaggtccaaa tccagctttt tggtgggtga 300 atggccaagg ggatgaagta aagtggagct tcagagagat gggagaccta acccgccgtg 360 tagccaacgt cttcacacag acctgtggcc tacaacaggg agaccatctg gccttgatgc 420 tgcctcgagt tcctgagtgg tggctggtgg ctgtgggctg catgcgaaca gggatcatct 480 tcattcctgc gaccatcctg ttgaaggcca aagacattct ctatcgacta cagttgtcta 540 aagccaaggg cattgtgacc atagatgccc ttgcctcaga ggtggactcc atagcttctc 600 agtgcccctc tctgaaaacc aagctcctgg tgtctgatca cagccgtgaa gggtggctgg 660 acttccgatc gctggttaaa tcagcatccc cagaacacac ctgtgttaag tcaaagacct 720 tggacccaat ggtcatcttc ttcaccagtg ggaccacagg cttccccaag atggcaaaac 780 actcccatgg gttggcctta caaccctcct tcccaggaag taggaaatta cggagcctga 840 agacatctga tgtctcctgg tgcctgtcgg actcaggatg gattgtggct accatttgga 900 ccctggtaga accatggaca gcgggttgta cagtctttat ccaccatctg ccacagtttg 960 acaccaaggt catcatacag acattgttga aataccccat taaccacttt tggggggtat 1020 catctatata tcgaatgatt ctgcagcagg atttcaccag catcaggttc cctgccctgg 1080 agcactgcta tactggcggg gaggtcgtgt tgcccaagga tcaggaggag tggaaaagac 1140 ggacgggcct tctgctctac gagaactatg ggcagtcgga aacgggacta atttgtgcca 1200 cctactgggg aatgaagatc aagccgggtt tcatggggaa ggccactcca ccctatgacg 1260 tccaggtcat tgatgacaag ggcagcatcc tgccacctaa cacagaagga aacattggca 1320 tcagaatcaa acctgtcagg cctgtgagcc tcttcatgtg ctatgagggt gacccagaga 1380 agacagctaa agtggaatgt ggggacttct acaacactgg ggacagagga aagatggatg 1440 aagagggcta catttgtttc ctggggagga gtgatgacat cattaatgcc tctgggtatc 1500 gcatcgggcc tgcagaggtt gaaagcgctt tggtggagca cccagcggtg gcggagtcag 1560 ccgtggtggg cagcccagac ccgattcgag gggaggtggt gaaggccttt attgtcctga 1620 ccccacagtt cctgtcccat gacaaggatc agctgaccaa ggaactgcag cagcatgtca 1680 agtcagtgac agccccatac aagtacccaa ggaacgtgga gtttgtctca gagctgccaa 1740 aaaccatcac tggcaagatt gaacggaagg aacttcggaa aaaggagact ggtcagatgt 1800 aatcggcagt gaactcagaa cgcactgcac acctaaggca aatccctggc cactttagtc 1860 tccccactat ggtgaggacg agggtggggc attgagagtg ttgatttggg aaagtatcag 1920 gagtgccata atcactagtg aattc 1945 38 577 PRT Homo Sapiens 38 Met Gln Trp Leu Met Arg Phe Arg Thr Leu Trp Gly Ile His Lys Ser 1 5 10 15 Phe His Asn Ile His Pro Ala Pro Ser Gln Leu Arg Cys Arg Ser Leu 20 25 30 Ser Glu Phe Gly Ala Pro Arg Trp Asn Asp Tyr Glu Val Pro Glu Glu 35 40 45 Phe Asn Phe Ala Ser Tyr Val Leu Asp Tyr Trp Ala Gln Lys Glu Lys 50 55 60 Glu Gly Lys Arg Gly Pro Asn Pro Ala Phe Trp Trp Val Asn Gly Gln 65 70 75 80 Gly Asp Glu Val Lys Trp Ser Phe Arg Glu Met Gly Asp Leu Thr Arg 85 90 95 Arg Val Ala Asn Val Phe Thr Gln Thr Cys Gly Leu Gln Gln Gly Asp 100 105 110 His Leu Ala Leu Met Leu Pro Arg Val Pro Glu Trp Trp Leu Val Ala 115 120 125 Val Gly Cys Met Arg Thr Gly Ile Ile Phe Ile Pro Ala Thr Ile Leu 130 135 140 Leu Lys Ala Lys Asp Ile Leu Tyr Arg Leu Gln Leu Ser Lys Ala Lys 145 150 155 160 Gly Ile Val Thr Ile Asp Ala Leu Ala Ser Glu Val Asp Ser Ile Ala 165 170 175 Ser Gln Cys Pro Ser Leu Lys Thr Lys Leu Leu Val Ser Asp His Ser 180 185 190 Arg Glu Gly Trp Leu Asp Phe Arg Ser Leu Val Lys Ser Ala Ser Pro 195 200 205 Glu His Thr Cys Val Lys Ser Lys Thr Leu Asp Pro Met Val Ile Phe 210 215 220 Phe Thr Ser Gly Thr Thr Gly Phe Pro Lys Met Ala Lys His Ser His 225 230 235 240 Gly Leu Ala Leu Gln Pro Ser Phe Pro Gly Ser Arg Lys Leu Arg Ser 245 250 255 Leu Lys Thr Ser Asp Val Ser Trp Cys Leu Ser Asp Ser Gly Trp Ile 260 265 270 Val Ala Thr Ile Trp Thr Leu Val Glu Pro Trp Thr Ala Gly Cys Thr 275 280 285 Val Phe Ile His His Leu Pro Gln Phe Asp Thr Lys Val Ile Ile Gln 290 295 300 Thr Leu Leu Lys Tyr Pro Ile Asn His Phe Trp Gly Val Ser Ser Ile 305 310 315 320 Tyr Arg Met Ile Leu Gln Gln Asp Phe Thr Ser Ile Arg Phe Pro Ala 325 330 335 Leu Glu His Cys Tyr Thr Gly Gly Glu Val Val Leu Pro Lys Asp Gln 340 345 350 Glu Glu Trp Lys Arg Arg Thr Gly Leu Leu Leu Tyr Glu Asn Tyr Gly 355 360 365 Gln Ser Glu Thr Gly Leu Ile Cys Ala Thr Tyr Trp Gly Met Lys Ile 370 375 380 Lys Pro Gly Phe Met Gly Lys Ala Thr Pro Pro Tyr Asp Val Gln Val 385 390 395 400 Ile Asp Asp Lys Gly Ser Ile Leu Pro Pro Asn Thr Glu Gly Asn Ile 405 410 415 Gly Ile Arg Ile Lys Pro Val Arg Pro Val Ser Leu Phe Met Cys Tyr 420 425 430 Glu Gly Asp Pro Glu Lys Thr Ala Lys Val Glu Cys Gly Asp Phe Tyr 435 440 445 Asn Thr Gly Asp Arg Gly Lys Met Asp Glu Glu Gly Tyr Ile Cys Phe 450 455 460 Leu Gly Arg Ser Asp Asp Ile Ile Asn Ala Ser Gly Tyr Arg Ile Gly 465 470 475 480 Pro Ala Glu Val Glu Ser Ala Leu Val Glu His Pro Ala Val Ala Glu 485 490 495 Ser Ala Val Val Gly Ser Pro Asp Pro Ile Arg Gly Glu Val Val Lys 500 505 510 Ala Phe Ile Val Leu Thr Pro Gln Phe Leu Ser His Asp Lys Asp Gln 515 520 525 Leu Thr Lys Glu Leu Gln Gln His Val Lys Ser Val Thr Ala Pro Tyr 530 535 540 Lys Tyr Pro Arg Asn Val Glu Phe Val Ser Glu Leu Pro Lys Thr Ile 545 550 555 560 Thr Gly Lys Ile Glu Arg Lys Glu Leu Arg Lys Lys Glu Thr Gly Gln 565 570 575 Met 39 3903 DNA Homo Sapiens 39 aatggtcagt caatacatta taacataata caccaaatgc tagaatagaa ggggaggggg 60 gcacacataa tgactcactg ctggaagaag ggtgcatcag tgaattaaaa aatgtccctc 120 ccctcttcag cactcagcgc gcagctattt ccttctgcca gtctctttga actctggatc 180 tttgcttttg ctcgctgctc tcctgttttt cattctccac attttctcaa tcctctttct 240 ttatccttag ccaccctgct tttttcctcc ttttttaaaa aatcggagat ttcgtcttaa 300 aatgatttgt cttccttacc ttcgtccatt tcaacactga aggctgcaaa gaacttcacc 360 tttcccctag tggtatttaa aaattctcaa tccgtaaaaa gtctttttga aaggcaaagg 420 aacaggaccc agaccctctc gacacccttg atccgagtca gatctgcact agcaaccaga 480 actaatattt catttaaccc accaaaaggg ggaggcgaga ggagccagaa gcaaacttca 540 tctgtctcag acggatccgt ggttcctaca tttggaggag ccgcgtgtca gaaggcgtag 600 gaccccaagg ggggacaagg aggactcccg agtctccctt ctccgctctc cgagaccgaa 660 gaggtggact gagccgctcg ggacagcggc accggaggag gctcggagaa gatgcggggc 720 tcggggcccc ggggtgcggg acaccggcgg cccccaagcg gcggcggcga cacccccatc 780 accccagcgt ccctggccgg ctgctactct gcacctcgac gggctcccct ctggacgtgc 840 cttctcctgt gcgccgcact ccggaccctc ctggccagcc ccagcaacga agtgaattta 900 ttggattcac gcactgtcat gggggacctg ggatggattg cttttccaaa aaatgggtgg 960 gaagagattg gtgaagtgga tgaaaattat gcccctatcc acacatacca agtatgcaaa 1020 gtgatggaac agaatcagaa taactggctt ttgaccagtt ggatctccaa tgaaggtgct 1080 tccagaatct tcatagaact caaatttacc ctgcgggact gcaacagcct tcctggagga 1140 ctggggacct gtaaggaaac ctttaatatg tattactttg agtcagatga tcagaatggg 1200 agaaacatca aggaaaacca atacatcaaa attgatacca ttgctgccga tgaaagcttt 1260 acagaacttg atcttggtga ccgtgttatg aaactgaata cagaggtcag agatgtagga 1320 cctctaagca aaaagggatt ttatcttgct tttcaagatg ttggtgcttg cattgctctg 1380 gtttctgtgc gtgtatacta taaaaaatgc ccttctgtgg tacgacactt ggctgtcttc 1440 cctgacacca tcactggagc tgattcttcc caattgctcg aagtgtcagg ctcctgtgtc 1500 aaccattctg tgaccgatga acctcccaaa atgcactgca gcgccgaagg ggagtggctg 1560 gtgcccatcg ggaaatgcat gtgcaaggca ggatatgaag agaaaaatgg cacctgtcaa 1620 gtgtgcagac ctgggttctt caaagcctca cctcacatcc agagctgcgg caaatgtcca 1680 cctcacagtt atacccatga ggaagcttca acctcttgtg tctgtgaaaa ggattatttc 1740 aggagagagt ctgatccacc cacaatggca tgcacaagac ccccctctgc tcctcggaat 1800 gccatctcaa atgttaatga aactagtgtc tttctggaat ggattccgcc tgctgacact 1860 ggtggaagga aagacgtgtc atattatatt gcatgcaaga agtgcaactc ccatgcaggt 1920 gtgtgtgagg agtgtggcgg tcatgtcagg taccttcccc ggcaaagcgg cctgaaaaac 1980 acctctgtca tgatggtgga tctactcgct cacacaaact atacctttga gattgaggca 2040 gtgaatggag tgtccgactt gagcccagga gcccggcagt atgtgtctgt aaatgtaacc 2100 acaaatcaag cagctccatc tccagtcacc aatgtgaaaa aagggaaaat tgcaaaaaac 2160 agcatctctt tgtcttggca agaaccagat cgtcccaatg gaatcatcct agagtatgaa 2220 atcaagcatt ttgaaaagga ccaagagacc agctacacga ttatcaaatc taaagagaca 2280 actattactg cagagggctt gaaaccagct tcagtttatg tcttccaaat tcgagcacgt 2340 acagcagcag gctatggtgt cttcagtcga agatttgagt ttgaaaccac cccagtgttt 2400 gcagcatcca gcgatcaaag ccagattcct gtaattgctg tgtctgtgac agtaggagtc 2460 attttgttgg cagtggttat cggcgtcctc ctcagtggaa gttgctgcga atgtggctgt 2520 gggagggctt cttccctgtg cgctgttgcc catccaatcc taatatggcg gtgtggctac 2580 agcaaagcaa aacaagatcc agaagaggaa aagatgcatt ttcataatgg gcacattaaa 2640 ctgccaggag taagaactta cattgatcca catacctatg aggatcccaa tcaagctgtc 2700 cacgaatttg ccaaggagat agaagcatca tgtatcacca ttgagagagt tattggagca 2760 ggtgaatttg gtgaagtttg tagtggacgt ttgaaactac caggaaaaag agaattacct 2820 gtggctatca aaacccttaa agtaggctat actgaaaagc aacgcagaga tttcctaggt 2880 gaagcaagta tcatgggaca gtttgatcat cctaacatca tccatttaga aggtgtggtg 2940 accaaaagta aaccagtgat gatcgtgaca gagtatatgg agaatggctc tttagataca 3000 tttttgaaga aaaacgatgg gcagttcact gtgattcagc ttgttggcat gctgagaggt 3060 atctctgcag gaatgaagta cctttctgac atgggctatg tgcatagaga tcttgctgcc 3120 agaaacatct taatcaacag taaccttgtg tgcaaagtgt ctgactttgg actttcccgg 3180 gtactggaag atgatcccga ggcagcctac accacaaggg gaggaaaaat tccaatcaga 3240 tggactgccc cagaagcaat agctttccga aagtttactt ctgccagtga tgtctggagt 3300 tatggaatag taatgtggga agttgtgtct tatggagaga gaccctactg ggagatgacc 3360 aatcaagatg tgattaaagc ggtagaggaa ggctatcgtc tgccaagccc catggattgt 3420 cctgctgctc tctatcagtt aatgctggat tgctggcaga aagagcgaaa tagcaggccc 3480 aagtttgatg aaatagtcaa catgttggac aagctgatac gtaacccaag tagtctgaag 3540 acgctggtta atgcatcctg cagagtatct aatttattgg cagaacatag cccactagga 3600 tctggggcct acagatcagt aggtgaatgg ctagaggcaa tcaagatggg ccggtataca 3660 gagattttca tggaaaatgg atacagttca atggacgctg tggctcaggt gaccttggag 3720 gatttgagac ggcttggagt gactcttgtc ggtcaccaga agaagatcat gaacagcctt 3780 caagaaatga aggtgcagct ggtaaacgga atggtgccat tgtaacttca tgtaaatgtc 3840 gcttcttcaa gtgaatgatt ctgcactttg taaacagcac tgagatttat tttaacaaaa 3900 aaa 3903 40 1037 PRT Homo Sapiens 40 Met Arg Gly Ser Gly Pro Arg Gly Ala Gly His Arg Arg Pro Pro Ser 1 5 10 15 Gly Gly Gly Asp Thr Pro Ile Thr Pro Ala Ser Leu Ala Gly Cys Tyr 20 25 30 Ser Ala Pro Arg Arg Ala Pro Leu Trp Thr Cys Leu Leu Leu Cys Ala 35 40 45 Ala Leu Arg Thr Leu Leu Ala Ser Pro Ser Asn Glu Val Asn Leu Leu 50 55 60 Asp Ser Arg Thr Val Met Gly Asp Leu Gly Trp Ile Ala Phe Pro Lys 65 70 75 80 Asn Gly Trp Glu Glu Ile Gly Glu Val Asp Glu Asn Tyr Ala Pro Ile 85 90 95 His Thr Tyr Gln Val Cys Lys Val Met Glu Gln Asn Gln Asn Asn Trp 100 105 110 Leu Leu Thr Ser Trp Ile Ser Asn Glu Gly Ala Ser Arg Ile Phe Ile 115 120 125 Glu Leu Lys Phe Thr Leu Arg Asp Cys Asn Ser Leu Pro Gly Gly Leu 130 135 140 Gly Thr Cys Lys Glu Thr Phe Asn Met Tyr Tyr Phe Glu Ser Asp Asp 145 150 155 160 Gln Asn Gly Arg Asn Ile Lys Glu Asn Gln Tyr Ile Lys Ile Asp Thr 165 170 175 Ile Ala Ala Asp Glu Ser Phe Thr Glu Leu Asp Leu Gly Asp Arg Val 180 185 190 Met Lys Leu Asn Thr Glu Val Arg Asp Val Gly Pro Leu Ser Lys Lys 195 200 205 Gly Phe Tyr Leu Ala Phe Gln Asp Val Gly Ala Cys Ile Ala Leu Val 210 215 220 Ser Val Arg Val Tyr Tyr Lys Lys Cys Pro Ser Val Val Arg His Leu 225 230 235 240 Ala Val Phe Pro Asp Thr Ile Thr Gly Ala Asp Ser Ser Gln Leu Leu 245 250 255 Glu Val Ser Gly Ser Cys Val Asn His Ser Val Thr Asp Glu Pro Pro 260 265 270 Lys Met His Cys Ser Ala Glu Gly Glu Trp Leu Val Pro Ile Gly Lys 275 280 285 Cys Met Cys Lys Ala Gly Tyr Glu Glu Lys Asn Gly Thr Cys Gln Val 290 295 300 Cys Arg Pro Gly Phe Phe Lys Ala Ser Pro His Ile Gln Ser Cys Gly 305 310 315 320 Lys Cys Pro Pro His Ser Tyr Thr His Glu Glu Ala Ser Thr Ser Cys 325 330 335 Val Cys Glu Lys Asp Tyr Phe Arg Arg Glu Ser Asp Pro Pro Thr Met 340 345 350 Ala Cys Thr Arg Pro Pro Ser Ala Pro Arg Asn Ala Ile Ser Asn Val 355 360 365 Asn Glu Thr Ser Val Phe Leu Glu Trp Ile Pro Pro Ala Asp Thr Gly 370 375 380 Gly Arg Lys Asp Val Ser Tyr Tyr Ile Ala Cys Lys Lys Cys Asn Ser 385 390 395 400 His Ala Gly Val Cys Glu Glu Cys Gly Gly His Val Arg Tyr Leu Pro 405 410 415 Arg Gln Ser Gly Leu Lys Asn Thr Ser Val Met Met Val Asp Leu Leu 420 425 430 Ala His Thr Asn Tyr Thr Phe Glu Ile Glu Ala Val Asn Gly Val Ser 435 440 445 Asp Leu Ser Pro Gly Ala Arg Gln Tyr Val Ser Val Asn Val Thr Thr 450 455 460 Asn Gln Ala Ala Pro Ser Pro Val Thr Asn Val Lys Lys Gly Lys Ile 465 470 475 480 Ala Lys Asn Ser Ile Ser Leu Ser Trp Gln Glu Pro Asp Arg Pro Asn 485 490 495 Gly Ile Ile Leu Glu Tyr Glu Ile Lys His Phe Glu Lys Asp Gln Glu 500 505 510 Thr Ser Tyr Thr Ile Ile Lys Ser Lys Glu Thr Thr Ile Thr Ala Glu 515 520 525 Gly Leu Lys Pro Ala Ser Val Tyr Val Phe Gln Ile Arg Ala Arg Thr 530 535 540 Ala Ala Gly Tyr Gly Val Phe Ser Arg Arg Phe Glu Phe Glu Thr Thr 545 550 555 560 Pro Val Phe Ala Ala Ser Ser Asp Gln Ser Gln Ile Pro Val Ile Ala 565 570 575 Val Ser Val Thr Val Gly Val Ile Leu Leu Ala Val Val Ile Gly Val 580 585 590 Leu Leu Ser Gly Ser Cys Cys Glu Cys Gly Cys Gly Arg Ala Ser Ser 595 600 605 Leu Cys Ala Val Ala His Pro Ile Leu Ile Trp Arg Cys Gly Tyr Ser 610 615 620 Lys Ala Lys Gln Asp Pro Glu Glu Glu Lys Met His Phe His Asn Gly 625 630 635 640 His Ile Lys Leu Pro Gly Val Arg Thr Tyr Ile Asp Pro His Thr Tyr 645 650 655 Glu Asp Pro Asn Gln Ala Val His Glu Phe Ala Lys Glu Ile Glu Ala 660 665 670 Ser Cys Ile Thr Ile Glu Arg Val Ile Gly Ala Gly Glu Phe Gly Glu 675 680 685 Val Cys Ser Gly Arg Leu Lys Leu Pro Gly Lys Arg Glu Leu Pro Val 690 695 700 Ala Ile Lys Thr Leu Lys Val Gly Tyr Thr Glu Lys Gln Arg Arg Asp 705 710 715 720 Phe Leu Gly Glu Ala Ser Ile Met Gly Gln Phe Asp His Pro Asn Ile 725 730 735 Ile His Leu Glu Gly Val Val Thr Lys Ser Lys Pro Val Met Ile Val 740 745 750 Thr Glu Tyr Met Glu Asn Gly Ser Leu Asp Thr Phe Leu Lys Lys Asn 755 760 765 Asp Gly Gln Phe Thr Val Ile Gln Leu Val Gly Met Leu Arg Gly Ile 770 775 780 Ser Ala Gly Met Lys Tyr Leu Ser Asp Met Gly Tyr Val His Arg Asp 785 790 795 800 Leu Ala Ala Arg Asn Ile Leu Ile Asn Ser Asn Leu Val Cys Lys Val 805 810 815 Ser Asp Phe Gly Leu Ser Arg Val Leu Glu Asp Asp Pro Glu Ala Ala 820 825 830 Tyr Thr Thr Arg Gly Gly Lys Ile Pro Ile Arg Trp Thr Ala Pro Glu 835 840 845 Ala Ile Ala Phe Arg Lys Phe Thr Ser Ala Ser Asp Val Trp Ser Tyr 850 855 860 Gly Ile Val Met Trp Glu Val Val Ser Tyr Gly Glu Arg Pro Tyr Trp 865 870 875 880 Glu Met Thr Asn Gln Asp Val Ile Lys Ala Val Glu Glu Gly Tyr Arg 885 890 895 Leu Pro Ser Pro Met Asp Cys Pro Ala Ala Leu Tyr Gln Leu Met Leu 900 905 910 Asp Cys Trp Gln Lys Glu Arg Asn Ser Arg Pro Lys Phe Asp Glu Ile 915 920 925 Val Asn Met Leu Asp Lys Leu Ile Arg Asn Pro Ser Ser Leu Lys Thr 930 935 940 Leu Val Asn Ala Ser Cys Arg Val Ser Asn Leu Leu Ala Glu His Ser 945 950 955 960 Pro Leu Gly Ser Gly Ala Tyr Arg Ser Val Gly Glu Trp Leu Glu Ala 965 970 975 Ile Lys Met Gly Arg Tyr Thr Glu Ile Phe Met Glu Asn Gly Tyr Ser 980 985 990 Ser Met Asp Ala Val Ala Gln Val Thr Leu Glu Asp Leu Arg Arg Leu 995 1000 1005 Gly Val Thr Leu Val Gly His Gln Lys Lys Ile Met Asn Ser Leu Gln 1010 1015 1020 Glu Met Lys Val Gln Leu Val Asn Gly Met Val Pro Leu 1025 1030 1035 41 2180 DNA Homo Sapiens 41 acgcgtccga gcgggccggc gtactggcct ggtccagcac ctgcggggcc ctcgggcttg 60 gagggctggg ccgggcgggg aacgggcggg gcgggccgga ggcggcggcg gctgactcgc 120 cttctctccg gggctgcgac cccgaggcaa ccggctgcag atgggagccc gcggagccga 180 ggatgcgggc gggccggggc gcgacgccgg cgagggagct gttccgggac gccgccttcc 240 ccgccgcgga ctcctcgctc ttctgcgact tgtctacgcc gctggcccag ttccgcgagg 300 acatcacgtg gaggcggccc caggagattt gtgccacacc ccggctgttt ccagatgacc 360 cacgggaagg gcaggtgaag caggggctgc tgggggattg ctggttcctg tgtgcctgcg 420 ccgcgctgca gaagagcagg cacctcctgg accaggtcat tcctccggga cagccgagct 480 gggccgacca ggagtaccgg ggctccttca cctgtcgcat ttggcagttt ggacgctggg 540 tggaggtgac cacagatgac cgcctgccgt gccttgcagg gagactctgt ttctcccgct 600 gccagaggga ggatgtgttc tggctcccct tactggaaaa ggtctacgcc aaggtccatg 660 ggtcctacga gcacctgtgg gccgggcagg tggcggatgc cctggtggac ctgaccggcg 720 gcctggcaga aagatggaac ctgaagggcg tagcaggaag cggaggccag caggacaggc 780 caggccgctg ggagcacagg acttgtcggc agctgctcca cctgaaggac cagtgtctga 840 tcagctgctg cgtgctcagc cccagagcag gtgcccggga gctgggggag ttccatgcct 900 tcattgtctc ggacctgcgg gagctccagg gtcaggcggg ccagtgcatc ctgctgctgc 960 ggatccagaa cccctggggc cggcggtgct ggcaggggct ctggagagag gggggtgaag 1020 ggtggagcca ggtagatgca gcggtagcat ctgagctcct gtcccagctc caggaagggg 1080 agttctgggt ggaggaggag gagttcctca gggagtttga cgagctcacc gttggctacc 1140 cggtcacgga ggccggccac ctgcagagcc tctacacaga gaggctgctc tgccatacgc 1200 gggcgctgcc tggggcctgg gtcaagggcc agtcagcagg aggctgccgg aacaacagcg 1260 gctttcccag caaccccaaa ttctggctgc gggtctcaga accgagtgag gtgtacattg 1320 ccgtcctgca gagatccagg ctgcacgcgg cggactgggc aggccgggcc cgggcactgg 1380 tgggtgacag tcatacttcg tggagcccag cgagcatccc gggcaagcac taccaggctg 1440 tgggtctgca cctctggaag gtcccagagg gtggaaggag ccaggacgca cccccactgc 1500 tgctgcagga gccgctgctg agctgcgtgc cacatcgcta cgcccaggag gtgagccggc 1560 tctgcctcct gcctgcgggc acctacaagg ttgtgccctc cacctacctg ccggacacag 1620 agggggcctt cacagtgacc atcgcaacca ggattgacag gccatccatt cacagccagg 1680 agatgctggg ccagttcctc caagaggtct ccgtcatggc agtgatgaaa acctaacagg 1740 gtggccccct gtgccagctc aggtgactgg agcccgaggg cctgacaggt tcccagcagc 1800 tgggccggcc agccttgcac tgtgggggct ggtcctgagt cttggcctgc ctcccagccc 1860 tgccaggggg ctgcggccta ggggtccacg ggaagcctcc gtcaggagag acgcagccct 1920 gggggccagc tggtgctgca aggaagggtg ggaagcttgc tggcttctgt tgcgccactg 1980 agacggcaga gaccccagga tcccagagct tcccaggatc cctcccagat cctctgctga 2040 ctccatatgg aggcctcaca cccagagggt agggcagcag atcttcttta taactattta 2100 ttgttcgaat cacttttagg atgtaacttt ataaataaac atgagcgctg atgatttgca 2160 aaaaaaaaaa aaaaaaaaaa 2180 42 517 PRT Homo Sapiens 42 Met Arg Ala Gly Arg Gly Ala Thr Pro Ala Arg Glu Leu Phe Arg Asp 1 5 10 15 Ala Ala Phe Pro Ala Ala Asp Ser Ser Leu Phe Cys Asp Leu Ser Thr 20 25 30 Pro Leu Ala Gln Phe Arg Glu Asp Ile Thr Trp Arg Arg Pro Gln Glu 35 40 45 Ile Cys Ala Thr Pro Arg Leu Phe Pro Asp Asp Pro Arg Glu Gly Gln 50 55 60 Val Lys Gln Gly Leu Leu Gly Asp Cys Trp Phe Leu Cys Ala Cys Ala 65 70 75 80 Ala Leu Gln Lys Ser Arg His Leu Leu Asp Gln Val Ile Pro Pro Gly 85 90 95 Gln Pro Ser Trp Ala Asp Gln Glu Tyr Arg Gly Ser Phe Thr Cys Arg 100 105 110 Ile Trp Gln Phe Gly Arg Trp Val Glu Val Thr Thr Asp Asp Arg Leu 115 120 125 Pro Cys Leu Ala Gly Arg Leu Cys Phe Ser Arg Cys Gln Arg Glu Asp 130 135 140 Val Phe Trp Leu Pro Leu Leu Glu Lys Val Tyr Ala Lys Val His Gly 145 150 155 160 Ser Tyr Glu His Leu Trp Ala Gly Gln Val Ala Asp Ala Leu Val Asp 165 170 175 Leu Thr Gly Gly Leu Ala Glu Arg Trp Asn Leu Lys Gly Val Ala Gly 180 185 190 Ser Gly Gly Gln Gln Asp Arg Pro Gly Arg Trp Glu His Arg Thr Cys 195 200 205 Arg Gln Leu Leu His Leu Lys Asp Gln Cys Leu Ile Ser Cys Cys Val 210 215 220 Leu Ser Pro Arg Ala Gly Ala Arg Glu Leu Gly Glu Phe His Ala Phe 225 230 235 240 Ile Val Ser Asp Leu Arg Glu Leu Gln Gly Gln Ala Gly Gln Cys Ile 245 250 255 Leu Leu Leu Arg Ile Gln Asn Pro Trp Gly Arg Arg Cys Trp Gln Gly 260 265 270 Leu Trp Arg Glu Gly Gly Glu Gly Trp Ser Gln Val Asp Ala Ala Val 275 280 285 Ala Ser Glu Leu Leu Ser Gln Leu Gln Glu Gly Glu Phe Trp Val Glu 290 295 300 Glu Glu Glu Phe Leu Arg Glu Phe Asp Glu Leu Thr Val Gly Tyr Pro 305 310 315 320 Val Thr Glu Ala Gly His Leu Gln Ser Leu Tyr Thr Glu Arg Leu Leu 325 330 335 Cys His Thr Arg Ala Leu Pro Gly Ala Trp Val Lys Gly Gln Ser Ala 340 345 350 Gly Gly Cys Arg Asn Asn Ser Gly Phe Pro Ser Asn Pro Lys Phe Trp 355 360 365 Leu Arg Val Ser Glu Pro Ser Glu Val Tyr Ile Ala Val Leu Gln Arg 370 375 380 Ser Arg Leu His Ala Ala Asp Trp Ala Gly Arg Ala Arg Ala Leu Val 385 390 395 400 Gly Asp Ser His Thr Ser Trp Ser Pro Ala Ser Ile Pro Gly Lys His 405 410 415 Tyr Gln Ala Val Gly Leu His Leu Trp Lys Val Pro Glu Gly Gly Arg 420 425 430 Ser Gln Asp Ala Pro Pro Leu Leu Leu Gln Glu Pro Leu Leu Ser Cys 435 440 445 Val Pro His Arg Tyr Ala Gln Glu Val Ser Arg Leu Cys Leu Leu Pro 450 455 460 Ala Gly Thr Tyr Lys Val Val Pro Ser Thr Tyr Leu Pro Asp Thr Glu 465 470 475 480 Gly Ala Phe Thr Val Thr Ile Ala Thr Arg Ile Asp Arg Pro Ser Ile 485 490 495 His Ser Gln Glu Met Leu Gly Gln Phe Leu Gln Glu Val Ser Val Met 500 505 510 Ala Val Met Lys Thr 515 43 1676 DNA Homo Sapiens 43 gtcaaatagc agccgcgggg aggctcgttc ccatcggcat ctgtgactgg ctgcgatcga 60 gggcccgggc ggccggccag ccgtctcgcc gagtgcggac tggccggatc tgctgtcagt 120 cagcgggaac agacttctcc ctctccatct ggtcaactgc gggagaaaaa ttttcgagaa 180 tttccagcag gcaaggcagt ggccgctttg actgcttgct tcggagatcc gagacgacgg 240 agaaggcact cttatttacc gaccaagaaa gctcctcccc cgtcctccgt tagctaatta 300 aaacattttt cagggacgta gccatccaga gacattccat tattgttcca ttgacctttc 360 cctcatcact gagtcctttg gagctgagtt atgtcaacag ctgccttaat tactttggtc 420 agaagtggtg ggaaccaggt gagaaggaga gtgctgctaa gctcccgcct gctgcaggac 480 gacaggcggg tgacacccac gtgccacagc tccacttcag agcctaggtg ttctcggttt 540 gacccagatg gtagtgggag tccagctacc tgggacaatt ttgggatctg ggataaccgc 600 attgatgagc caattctgct gccacccagc attaagtatg gcaagccaat tcccaaaatc 660 agcttggaaa atgtggggtg cgcctcacag attggcaaac ggaaagagaa tgaagatcgg 720 tttgacttcg ctcagctgac agatgaggtc ctgtactttg cagtgtatga tggacacggt 780 ggacctgcag cagctgattt ctgtcatacc cacatggaga aatgtattat ggatttgctt 840 cctaaggaga agaacttgga aactctgttg accttggctt ttctagaaat agataaagcc 900 ttttcgagtc atgcccgcct gtctgctgat gcaactcttc tgacctctgg gactactgca 960 acagtagccc tattgcgaga tggtattgaa ctggttgtag ccagtgttgg ggacagccgg 1020 gctattttgt gtagaaaagg aaaacccatg aagctgacca ttgaccatac tccagaaaga 1080 aaagatgaaa aagaaaggat caagaaatgt ggtggttttg tagcttggaa tagtttgggg 1140 cagcctcacg taaatggcag gcttgcaatg acaagaagta ttggagattt ggaccttaag 1200 accagtggtg tcatagcaga acctgaaact aagaggatta agttacatca tgctgatgac 1260 agcttcctgg tcctcaccac agatggaatt aacttcatgg tgaatagtca agagatttgt 1320 gactttgtca atcagtgcca tgatcccaac gaagcagccc atgcggtgac tgaacaggtg 1380 acccagagct tctgcctgaa aagtcccaag gagaaggaag gaaaggacag tccaggcatt 1440 gtgttttagc ttttgagtgt tgcagtgaat tttacacttg attccataat atttccaatt 1500 ataaaatttt tatttcccca agttaaaatt ttaatatgcc aaggaaatgt gctttgttta 1560 ttctttgact ttgtatatac cttgaaatga tagtaacagc aatagtaaat tataatagta 1620 aactaatatt cacttgctat gtgtcagaca atattcatat gtattagctc attact 1676 44 352 PRT Homo Sapiens 44 Met Ser Thr Ala Ala Leu Ile Thr Leu Val Arg Ser Gly Gly Asn Gln 1 5 10 15 Val Arg Arg Arg Val Leu Leu Ser Ser Arg Leu Leu Gln Asp Asp Arg 20 25 30 Arg Val Thr Pro Thr Cys His Ser Ser Thr Ser Glu Pro Arg Cys Ser 35 40 45 Arg Phe Asp Pro Asp Gly Ser Gly Ser Pro Ala Thr Trp Asp Asn Phe 50 55 60 Gly Ile Trp Asp Asn Arg Ile Asp Glu Pro Ile Leu Leu Pro Pro Ser 65 70 75 80 Ile Lys Tyr Gly Lys Pro Ile Pro Lys Ile Ser Leu Glu Asn Val Gly 85 90 95 Cys Ala Ser Gln Ile Gly Lys Arg Lys Glu Asn Glu Asp Arg Phe Asp 100 105 110 Phe Ala Gln Leu Thr Asp Glu Val Leu Tyr Phe Ala Val Tyr Asp Gly 115 120 125 His Gly Gly Pro Ala Ala Ala Asp Phe Cys His Thr His Met Glu Lys 130 135 140 Cys Ile Met Asp Leu Leu Pro Lys Glu Lys Asn Leu Glu Thr Leu Leu 145 150 155 160 Thr Leu Ala Phe Leu Glu Ile Asp Lys Ala Phe Ser Ser His Ala Arg 165 170 175 Leu Ser Ala Asp Ala Thr Leu Leu Thr Ser Gly Thr Thr Ala Thr Val 180 185 190 Ala Leu Leu Arg Asp Gly Ile Glu Leu Val Val Ala Ser Val Gly Asp 195 200 205 Ser Arg Ala Ile Leu Cys Arg Lys Gly Lys Pro Met Lys Leu Thr Ile 210 215 220 Asp His Thr Pro Glu Arg Lys Asp Glu Lys Glu Arg Ile Lys Lys Cys 225 230 235 240 Gly Gly Phe Val Ala Trp Asn Ser Leu Gly Gln Pro His Val Asn Gly 245 250 255 Arg Leu Ala Met Thr Arg Ser Ile Gly Asp Leu Asp Leu Lys Thr Ser 260 265 270 Gly Val Ile Ala Glu Pro Glu Thr Lys Arg Ile Lys Leu His His Ala 275 280 285 Asp Asp Ser Phe Leu Val Leu Thr Thr Asp Gly Ile Asn Phe Met Val 290 295 300 Asn Ser Gln Glu Ile Cys Asp Phe Val Asn Gln Cys His Asp Pro Asn 305 310 315 320 Glu Ala Ala His Ala Val Thr Glu Gln Val Thr Gln Ser Phe Cys Leu 325 330 335 Lys Ser Pro Lys Glu Lys Glu Gly Lys Asp Ser Pro Gly Ile Val Phe 340 345 350 45 1680 DNA Homo Sapiens 45 atgattgtcc catcggtact agaaagtgaa gtcattgctc caattttgga agaggagaga 60 ataactggct gaggggtgag aaagacagaa atagctgcag ctctcttttt tttttcaaca 120 aaggctccag cctgggcaac aaagtaagat cctgtctcaa aagaaaaaaa aaaaaggtga 180 agctgaaccc agatctacac atacagctaa tcttaccaaa atgtgtggaa gtaaagcaat 240 ctgaaggaaa ttcagtacca tacaatttac tgactgagat acatcatatt gctcatacta 300 agaataagag tggagaagaa tcattttttt cctgctaaaa tgatagaggc agaagagcaa 360 cagccttgca agatagactt ctattctgaa ttgccaaaag tggaacttca tgcccacttg 420 aatggatcca ttagttctca taccatgaag aaattaatag cccagaagcc agatcttaaa 480 atccacgatc agatgactgt gattgacaag ggaaagaaaa gaactttgga agaatgtttc 540 cagatgtttc aaactattca tcagcttact agtagccctg aagatattct aatggtcaca 600 aaagatgtca taaaagaatt tgcagatgac ggcgtcaagt acctggaact aaggagcaca 660 cccagaagag aaaatgctac tggaatgact aaaaagactt atgtggaatc tatacttgaa 720 ggtataaaac agtccaaaca agaaaacttg gacattgatg ttaggtattt gatagcagtt 780 gacagaagag gtggcccttt agtagccaag gagactgtaa aacttgccga ggagttcttc 840 ctttctactg agggtacagt tcttggcctt gacctcagtg gagaccctac tgtaggacaa 900 gcaaaagact tcttggaacc tcttttagaa gctaagaaag caggtctgaa gttagcattg 960 catctttcag agattccaaa ccaaaaaaaa gaaacacaaa tactcctgga tctgcttcct 1020 gacagaatcg ggcatggaac atttctcaac tccggtgagg gaggatccct ggatctggtg 1080 gactttgtga ggcaacatcg gataccactg gaactctgtt tgacctcaaa cgtcaaaagt 1140 cagacagttc catcttatga ccagcaccat ttcggattct ggtacagcat tgcccatcct 1200 tctgtgatct gtactgatga taagggtgtt tttgcaacac acctttctca agagtaccag 1260 ctggcagctg aaacatttaa tttgacccag tctcaggtgt gggatctgtc ttatgaatcc 1320 atcaactaca tctttgcttc tgacagcacc agatctgaac tgaggaagaa atggaatcac 1380 ctgaagccca gagtgttaca tatttaagct ataatgaggt gaactacttc tgagtatgtg 1440 tttcaatcaa gttcctgcca tatcccactt agtaaaacag tccaccactc ctttgaagca 1500 tagcaaccaa gttccttggg ctctatcacc agcaccttac acatggcagg tactcagtaa 1560 atacgtgtct tcaactgact cacaagctct caggtgctta ctgggtggga cttgactgtt 1620 gttgctaatt aaatccccat tccaccagtg aaaaaaaaaa aaaaaaaaaa gggcggccgc 1680 46 355 PRT Homo Sapiens 46 Met Ile Glu Ala Glu Glu Gln Gln Pro Cys Lys Ile Asp Phe Tyr Ser 1 5 10 15 Glu Leu Pro Lys Val Glu Leu His Ala His Leu Asn Gly Ser Ile Ser 20 25 30 Ser His Thr Met Lys Lys Leu Ile Ala Gln Lys Pro Asp Leu Lys Ile 35 40 45 His Asp Gln Met Thr Val Ile Asp Lys Gly Lys Lys Arg Thr Leu Glu 50 55 60 Glu Cys Phe Gln Met Phe Gln Thr Ile His Gln Leu Thr Ser Ser Pro 65 70 75 80 Glu Asp Ile Leu Met Val Thr Lys Asp Val Ile Lys Glu Phe Ala Asp 85 90 95 Asp Gly Val Lys Tyr Leu Glu Leu Arg Ser Thr Pro Arg Arg Glu Asn 100 105 110 Ala Thr Gly Met Thr Lys Lys Thr Tyr Val Glu Ser Ile Leu Glu Gly 115 120 125 Ile Lys Gln Ser Lys Gln Glu Asn Leu Asp Ile Asp Val Arg Tyr Leu 130 135 140 Ile Ala Val Asp Arg Arg Gly Gly Pro Leu Val Ala Lys Glu Thr Val 145 150 155 160 Lys Leu Ala Glu Glu Phe Phe Leu Ser Thr Glu Gly Thr Val Leu Gly 165 170 175 Leu Asp Leu Ser Gly Asp Pro Thr Val Gly Gln Ala Lys Asp Phe Leu 180 185 190 Glu Pro Leu Leu Glu Ala Lys Lys Ala Gly Leu Lys Leu Ala Leu His 195 200 205 Leu Ser Glu Ile Pro Asn Gln Lys Lys Glu Thr Gln Ile Leu Leu Asp 210 215 220 Leu Leu Pro Asp Arg Ile Gly His Gly Thr Phe Leu Asn Ser Gly Glu 225 230 235 240 Gly Gly Ser Leu Asp Leu Val Asp Phe Val Arg Gln His Arg Ile Pro 245 250 255 Leu Glu Leu Cys Leu Thr Ser Asn Val Lys Ser Gln Thr Val Pro Ser 260 265 270 Tyr Asp Gln His His Phe Gly Phe Trp Tyr Ser Ile Ala His Pro Ser 275 280 285 Val Ile Cys Thr Asp Asp Lys Gly Val Phe Ala Thr His Leu Ser Gln 290 295 300 Glu Tyr Gln Leu Ala Ala Glu Thr Phe Asn Leu Thr Gln Ser Gln Val 305 310 315 320 Trp Asp Leu Ser Tyr Glu Ser Ile Asn Tyr Ile Phe Ala Ser Asp Ser 325 330 335 Thr Arg Ser Glu Leu Arg Lys Lys Trp Asn His Leu Lys Pro Arg Val 340 345 350 Leu His Ile 355 47 1835 DNA Homo Sapiens 47 ggagctgcgg gctgcgtggc cgggatgagc gccagcacgg gcggtggtgg ggacagcggc 60 ggcagcggcg gcagtagcag cagctcacag gcctcctgcg ggcccgagtc ctcgggctcc 120 gaactagccc tggccacacc ggtgcctcag atgctgcagg gccttctggg ctccgacgac 180 gaggaacagg aagaccccaa agactactgc aagggcggct accaccctgt gaagatcggc 240 gacgtgttca atgggcggta ccacgtggtg cgcaaactgg gctggggcca cttctccacc 300 gtctggctct gctgggacat ccagcgcaag cgctttgtgg ccctcaaagt ggtgaagagt 360 gcggggcatt acacggagac agctgtggat gagatcaagc tcctgaaatg tgtccgggac 420 agcgacccca gtgaccccaa aagagagacc attgtccagc tcattgatga cttcaggatc 480 tcaggagtca atggagtcca tgtgtgcatg gtgctggagg tgctgggcca ccagctcctc 540 aaatggatca tcaagtccaa ctaccagggc ctgcccgtgc cctgcgtgaa gagcatcgtg 600 aggcaggtgc tgcacggcct ggactacctc cacaccaagt gcaagatcat ccacacggac 660 atcaagcccg agaacatctt gctgtgtgtg ggggacgctt acatcaggcg cctggctgcc 720 gaggccacgg agtggcaaca ggcaggggcg ccgcccccct cccgctccat agtcagcact 780 gccccccagg aggtcttgac cggtaagctg tccaaaaaca agaggaagaa gatgaggcgc 840 aaacggaaac agcagaagcg gctgctggag gagcggctgc gggacctgca gaggctggag 900 gccatggagg ctgccaccca ggctgaggac tctggcttga gactagacgg gggcagcggc 960 tccacatcct cttcaggctt ctccggctcc ctcttctctc ctgcctcctg ctccatcctc 1020 tccggctcgt ccaatcagcg agagaccggg ggcctcctgt cgcctagcac accattcggt 1080 gcctcgaacc tcctggtgaa ccccctggag ccccaaaatg cagataagat caagatcaag 1140 atcgcagacc tgggcaacgc ctgctgggtg cacaagcact tcacggaaga catccagact 1200 cggcagtacc gggccgtcga ggtgctgatc ggcgccgaat acggcccccc ggcagacatc 1260 tggagcacag cctgcatggc cttcgagctg gccactggtg actacctgtt cgagccgcat 1320 tctggagaag actacagtcg tgatgaggac cacatcgctc acatagtgga gcttctgggg 1380 gacatccccc cagccttcgc cctctcaggc cgctattccc gggagttctt caaccggaga 1440 ggagagctgc ggcacatcca caatctcaag cactggggcc tgtacgaggt actcatggaa 1500 aagtacgagt ggcccctaga gcaggccaca cagttcagcg cctttctgct gcccatgatg 1560 gagtacatcc ccgaaaagcg ggccagtgcc gctgactgcc tccagcaccc ctggctcaac 1620 ccctaggccc ggctgtggct ccacctccag ctctccgtgc cttaagggaa aagcgggaca 1680 gctcccacca ccctgctggg cgccagttct ccacaaccac agggcagaga gacgctggag 1740 ccaggcccgg ctctcagagc gtgttctgcc tgagaccccc gtgagggctc tcggagaaag 1800 tgtgtgtatt cctttcttaa taaagtgtgg actga 1835 48 533 PRT Homo Sapiens 48 Met Ser Ala Ser Thr Gly Gly Gly Gly Asp Ser Gly Gly Ser Gly Gly 1 5 10 15 Ser Ser Ser Ser Ser Gln Ala Ser Cys Gly Pro Glu Ser Ser Gly Ser 20 25 30 Glu Leu Ala Leu Ala Thr Pro Val Pro Gln Met Leu Gln Gly Leu Leu 35 40 45 Gly Ser Asp Asp Glu Glu Gln Glu Asp Pro Lys Asp Tyr Cys Lys Gly 50 55 60 Gly Tyr His Pro Val Lys Ile Gly Asp Val Phe Asn Gly Arg Tyr His 65 70 75 80 Val Val Arg Lys Leu Gly Trp Gly His Phe Ser Thr Val Trp Leu Cys 85 90 95 Trp Asp Ile Gln Arg Lys Arg Phe Val Ala Leu Lys Val Val Lys Ser 100 105 110 Ala Gly His Tyr Thr Glu Thr Ala Val Asp Glu Ile Lys Leu Leu Lys 115 120 125 Cys Val Arg Asp Ser Asp Pro Ser Asp Pro Lys Arg Glu Thr Ile Val 130 135 140 Gln Leu Ile Asp Asp Phe Arg Ile Ser Gly Val Asn Gly Val His Val 145 150 155 160 Cys Met Val Leu Glu Val Leu Gly His Gln Leu Leu Lys Trp Ile Ile 165 170 175 Lys Ser Asn Tyr Gln Gly Leu Pro Val Pro Cys Val Lys Ser Ile Val 180 185 190 Arg Gln Val Leu His Gly Leu Asp Tyr Leu His Thr Lys Cys Lys Ile 195 200 205 Ile His Thr Asp Ile Lys Pro Glu Asn Ile Leu Leu Cys Val Gly Asp 210 215 220 Ala Tyr Ile Arg Arg Leu Ala Ala Glu Ala Thr Glu Trp Gln Gln Ala 225 230 235 240 Gly Ala Pro Pro Pro Ser Arg Ser Ile Val Ser Thr Ala Pro Gln Glu 245 250 255 Val Leu Thr Gly Lys Leu Ser Lys Asn Lys Arg Lys Lys Met Arg Arg 260 265 270 Lys Arg Lys Gln Gln Lys Arg Leu Leu Glu Glu Arg Leu Arg Asp Leu 275 280 285 Gln Arg Leu Glu Ala Met Glu Ala Ala Thr Gln Ala Glu Asp Ser Gly 290 295 300 Leu Arg Leu Asp Gly Gly Ser Gly Ser Thr Ser Ser Ser Gly Phe Ser 305 310 315 320 Gly Ser Leu Phe Ser Pro Ala Ser Cys Ser Ile Leu Ser Gly Ser Ser 325 330 335 Asn Gln Arg Glu Thr Gly Gly Leu Leu Ser Pro Ser Thr Pro Phe Gly 340 345 350 Ala Ser Asn Leu Leu Val Asn Pro Leu Glu Pro Gln Asn Ala Asp Lys 355 360 365 Ile Lys Ile Lys Ile Ala Asp Leu Gly Asn Ala Cys Trp Val His Lys 370 375 380 His Phe Thr Glu Asp Ile Gln Thr Arg Gln Tyr Arg Ala Val Glu Val 385 390 395 400 Leu Ile Gly Ala Glu Tyr Gly Pro Pro Ala Asp Ile Trp Ser Thr Ala 405 410 415 Cys Met Ala Phe Glu Leu Ala Thr Gly Asp Tyr Leu Phe Glu Pro His 420 425 430 Ser Gly Glu Asp Tyr Ser Arg Asp Glu Asp His Ile Ala His Ile Val 435 440 445 Glu Leu Leu Gly Asp Ile Pro Pro Ala Phe Ala Leu Ser Gly Arg Tyr 450 455 460 Ser Arg Glu Phe Phe Asn Arg Arg Gly Glu Leu Arg His Ile His Asn 465 470 475 480 Leu Lys His Trp Gly Leu Tyr Glu Val Leu Met Glu Lys Tyr Glu Trp 485 490 495 Pro Leu Glu Gln Ala Thr Gln Phe Ser Ala Phe Leu Leu Pro Met Met 500 505 510 Glu Tyr Ile Pro Glu Lys Arg Ala Ser Ala Ala Asp Cys Leu Gln His 515 520 525 Pro Trp Leu Asn Pro 530 49 1247 DNA Homo Sapiens 49 cacgcgtccg tgagcctggg cacccctctc tgttctcgca gagatgcccg gcaaacagtc 60 tgaggaaggg ccggcggagg caggggcttc ggaggacagc gaggaggagg gtctgggcgg 120 cctgacatta gaggagctcc agcagggcca ggaggctgcc cgcgcgctgg aggacatgat 180 gacgctgagt gctcagaccc tggtccgagc cgaggtggac gagctctacg aggaagtgcg 240 tcccctgggc cagggtcgct atggccgcgt ccttctggtc acccatcgtc agaaaggcac 300 acccctggca ctgaagcagc tcccgaaacc ccgcacgtcc ctccgtggct tcctgtacga 360 gttctgtgtg gggctctcgc tgggcgcgca ctcagccatc gtgacggcct acggcattgg 420 catcgagtcg gcacactcct acagcttcct gacggagccc gtcctgcacg gggacctcat 480 ggccttcatc cagcccaagg tgggcctccc gcagcccgcg gtgcaccgct gcgccgccca 540 gctggcctcc gccctggagt acatccacgc ccgcggcctg gtgtaccggg acctgaagcc 600 ggagaacgtc ctggtgtgcg acccggcctg ccggcgcttc aagctgaccg acttcggcca 660 cacgaggcct cgcgggacgc tgctgcgcct ggccgggccg cccatcccct acacggcccc 720 cgagctctgc gcgcccccgc cgctccccga gggcctgccc attcagcccg ccctggacgc 780 ctgggcgctg ggcgtcctgc tcttctgcct cctcacgggc tacttcccct gggaccggcc 840 cctggccgag gccgacccct tctacgagga cttcctcatc tggcaggcgt cgggccagcc 900 ccgggaccgc cctcagccct ggttcggcct ggcccccgcg gccgacgcgc ttctgcgggg 960 gctgctggac cctcaccccc gaaggaggag cgctgtgatc gccatcaggg agcacctggg 1020 gcgcccctgg aggcagcggg agggcgaggc ggaggcagtg ggagcggtgg aagaggaggc 1080 tgggcagtga ggaggccccg ggggatgcag aaagggaagc cgccccaccc gaggccccca 1140 agttcaacgg cttttggtgt ctcctcggtg tgttttcatc catggggctt gggattcccc 1200 tcggcgtcct cctcctctct cctcacctgc ccgggcggcc gctcgag 1247 50 348 PRT Homo Sapiens 50 Met Pro Gly Lys Gln Ser Glu Glu Gly Pro Ala Glu Ala Gly Ala Ser 1 5 10 15 Glu Asp Ser Glu Glu Glu Gly Leu Gly Gly Leu Thr Leu Glu Glu Leu 20 25 30 Gln Gln Gly Gln Glu Ala Ala Arg Ala Leu Glu Asp Met Met Thr Leu 35 40 45 Ser Ala Gln Thr Leu Val Arg Ala Glu Val Asp Glu Leu Tyr Glu Glu 50 55 60 Val Arg Pro Leu Gly Gln Gly Arg Tyr Gly Arg Val Leu Leu Val Thr 65 70 75 80 His Arg Gln Lys Gly Thr Pro Leu Ala Leu Lys Gln Leu Pro Lys Pro 85 90 95 Arg Thr Ser Leu Arg Gly Phe Leu Tyr Glu Phe Cys Val Gly Leu Ser 100 105 110 Leu Gly Ala His Ser Ala Ile Val Thr Ala Tyr Gly Ile Gly Ile Glu 115 120 125 Ser Ala His Ser Tyr Ser Phe Leu Thr Glu Pro Val Leu His Gly Asp 130 135 140 Leu Met Ala Phe Ile Gln Pro Lys Val Gly Leu Pro Gln Pro Ala Val 145 150 155 160 His Arg Cys Ala Ala Gln Leu Ala Ser Ala Leu Glu Tyr Ile His Ala 165 170 175 Arg Gly Leu Val Tyr Arg Asp Leu Lys Pro Glu Asn Val Leu Val Cys 180 185 190 Asp Pro Ala Cys Arg Arg Phe Lys Leu Thr Asp Phe Gly His Thr Arg 195 200 205 Pro Arg Gly Thr Leu Leu Arg Leu Ala Gly Pro Pro Ile Pro Tyr Thr 210 215 220 Ala Pro Glu Leu Cys Ala Pro Pro Pro Leu Pro Glu Gly Leu Pro Ile 225 230 235 240 Gln Pro Ala Leu Asp Ala Trp Ala Leu Gly Val Leu Leu Phe Cys Leu 245 250 255 Leu Thr Gly Tyr Phe Pro Trp Asp Arg Pro Leu Ala Glu Ala Asp Pro 260 265 270 Phe Tyr Glu Asp Phe Leu Ile Trp Gln Ala Ser Gly Gln Pro Arg Asp 275 280 285 Arg Pro Gln Pro Trp Phe Gly Leu Ala Pro Ala Ala Asp Ala Leu Leu 290 295 300 Arg Gly Leu Leu Asp Pro His Pro Arg Arg Arg Ser Ala Val Ile Ala 305 310 315 320 Ile Arg Glu His Leu Gly Arg Pro Trp Arg Gln Arg Glu Gly Glu Ala 325 330 335 Glu Ala Val Gly Ala Val Glu Glu Glu Ala Gly Gln 340 345 51 1881 DNA Homo Sapiens 51 gttatttctt caaaaggaaa acacaatttt cttttatatc aaaacaatgc aaacttgatg 60 gttcttaatt ctacattttc tattaatagt ttacaaactt aaaaattaaa ctaagtacac 120 aattgaaaga tttttttttc ttacaaagaa cacgttatac gtcatttaaa ttgccaaata 180 tcaaatagtt tattctattt cactttctag ggaaaaaaac caactgctcc aaaagaatgt 240 gtttttctcc cattctggaa atcaacatgc agtctgaatc taacattaca gtgcgagatg 300 acattgatga catcaacacc aatatgtacc aaccactatc atatccgtta agctttcaag 360 tgtctctcac cggatttctt atgttagaaa ttgtgttggg acttggcagc aacctcactg 420 tattggtact ttactgcatg aaatccaact taatcaactc tgtcagtaac attattacaa 480 tgaatcttca tgtacttgat gtaataattt gtgtgggatg tattcctcta actatagtta 540 tccttctgct ttcactggag agtaacactg ctctcatttg ctgtttccat gaggcttgtg 600 tatcttttgc aagtgtctca acagcaatca acgtttttgc tatcactttg gacagatatg 660 acatctctgt aaaacctgca aaccgaattc tgacaatggg cagagctgta atgttaatga 720 tatccatttg gattttttct tttttctctt tcctgattcc ttttattgag gtaaattttt 780 tcagtcttca aagtggaaat acctgggaaa acaagacact tttatgtgtc agtacaaatg 840 aatactacac tgaactggga atgtattatc acctgttagt acagatccca atattctttt 900 tcactgttgt agtaatgtta atcacataca ccaaaatact tcaggctctt aatattcgaa 960 taggcacaag attttcaaca gggcagaaga agaaagcaag aaagaaaaag acaatttctc 1020 taaccacaca acatgaggct acagacatgt cacaaagcag tggtgggaga aatgtagtct 1080 ttggtgtaag aacttcagtt tctgtaataa ttgccctccg gcgagctgtg aaacgacacc 1140 gtgaacgacg agaaagacaa aagagagtct tcaggatgtc tttattgatt atttctacat 1200 ttcttctctg ctggacacca atttctgttt taaataccac cattttatgt ttaggcccaa 1260 gtgacctttt agtaaaatta agattgtgtt ttttagtcat ggcttatgga acaactatat 1320 ttcaccctct attatatgca ttcactagac aaaaatttca aaaggtcttg aaaagtaaaa 1380 tgaaaaagcg agttgtttct atagtagaag ctgatcccct gcctaataat gctgtaatac 1440 acaactcttg gatagatccc aaaagaaaca aaaaaattac ctttgaagat agtgaaataa 1500 gagaaaaacg tttagtgcct caggttgtca cagactagag aaaagtctca gtttcaccaa 1560 atccacattc aaatgagttt taaatttaaa ttgtaaaaac tgatattact gccaaatata 1620 agaaaaatat tttaagtatt ggttatgttg taaattttca atgtgaaatg ctaattagat 1680 aggtcatata tattcaattt cttcattact taatgtattt gttgcatggc agtttgttaa 1740 agtactatca tgtgtatatt ttgtcaatat tatgtccaac agaaaatatt catgtaagtc 1800 atatttttta aggaataaat acatagcctt aaaacagtgt ataactttaa aatgtaaaaa 1860 aaaaaaaaaa aaaaaaaaaa a 1881 52 433 PRT Homo Sapiens 52 Met Cys Phe Ser Pro Ile Leu Glu Ile Asn Met Gln Ser Glu Ser Asn 1 5 10 15 Ile Thr Val Arg Asp Asp Ile Asp Asp Ile Asn Thr Asn Met Tyr Gln 20 25 30 Pro Leu Ser Tyr Pro Leu Ser Phe Gln Val Ser Leu Thr Gly Phe Leu 35 40 45 Met Leu Glu Ile Val Leu Gly Leu Gly Ser Asn Leu Thr Val Leu Val 50 55 60 Leu Tyr Cys Met Lys Ser Asn Leu Ile Asn Ser Val Ser Asn Ile Ile 65 70 75 80 Thr Met Asn Leu His Val Leu Asp Val Ile Ile Cys Val Gly Cys Ile 85 90 95 Pro Leu Thr Ile Val Ile Leu Leu Leu Ser Leu Glu Ser Asn Thr Ala 100 105 110 Leu Ile Cys Cys Phe His Glu Ala Cys Val Ser Phe Ala Ser Val Ser 115 120 125 Thr Ala Ile Asn Val Phe Ala Ile Thr Leu Asp Arg Tyr Asp Ile Ser 130 135 140 Val Lys Pro Ala Asn Arg Ile Leu Thr Met Gly Arg Ala Val Met Leu 145 150 155 160 Met Ile Ser Ile Trp Ile Phe Ser Phe Phe Ser Phe Leu Ile Pro Phe 165 170 175 Ile Glu Val Asn Phe Phe Ser Leu Gln Ser Gly Asn Thr Trp Glu Asn 180 185 190 Lys Thr Leu Leu Cys Val Ser Thr Asn Glu Tyr Tyr Thr Glu Leu Gly 195 200 205 Met Tyr Tyr His Leu Leu Val Gln Ile Pro Ile Phe Phe Phe Thr Val 210 215 220 Val Val Met Leu Ile Thr Tyr Thr Lys Ile Leu Gln Ala Leu Asn Ile 225 230 235 240 Arg Ile Gly Thr Arg Phe Ser Thr Gly Gln Lys Lys Lys Ala Arg Lys 245 250 255 Lys Lys Thr Ile Ser Leu Thr Thr Gln His Glu Ala Thr Asp Met Ser 260 265 270 Gln Ser Ser Gly Gly Arg Asn Val Val Phe Gly Val Arg Thr Ser Val 275 280 285 Ser Val Ile Ile Ala Leu Arg Arg Ala Val Lys Arg His Arg Glu Arg 290 295 300 Arg Glu Arg Gln Lys Arg Val Phe Arg Met Ser Leu Leu Ile Ile Ser 305 310 315 320 Thr Phe Leu Leu Cys Trp Thr Pro Ile Ser Val Leu Asn Thr Thr Ile 325 330 335 Leu Cys Leu Gly Pro Ser Asp Leu Leu Val Lys Leu Arg Leu Cys Phe 340 345 350 Leu Val Met Ala Tyr Gly Thr Thr Ile Phe His Pro Leu Leu Tyr Ala 355 360 365 Phe Thr Arg Gln Lys Phe Gln Lys Val Leu Lys Ser Lys Met Lys Lys 370 375 380 Arg Val Val Ser Ile Val Glu Ala Asp Pro Leu Pro Asn Asn Ala Val 385 390 395 400 Ile His Asn Ser Trp Ile Asp Pro Lys Arg Asn Lys Lys Ile Thr Phe 405 410 415 Glu Asp Ser Glu Ile Arg Glu Lys Arg Leu Val Pro Gln Val Val Thr 420 425 430 Asp 53 1626 DNA Homo Sapiens misc_feature (1)...(1626) n = A,T,C or G 53 aggtcccggg atccggtggg tggtgcaaat caaagaacct gctcctcagt ggatgttgcc 60 ctttactttc taggccttgt ccgggaagtg ttactnnnnn nnnnnnnnnn nnnnnnnnnn 120 nnnnnnnnnn nnnnnnnnnn nnnnnnnnac gcgtccgccg gccgctgggc cgctgcctga 180 gccagggagg cgcagcgcga gctcccactt cgtcttcatg gattcccagc ccagctgcgt 240 ggtggtgact ggttttgggc ccttccggca gcacttggtg aattccagct gggaagcagt 300 gaaggagctc tccaagctgg gcctggggaa tgaaacagtg gtgcagctgc ggactctgga 360 gctgcctgta gattacaggg aggctaagcg gagggtcacc ggaatctggg aagatcatca 420 gccgcaactc gtcgtgcatg tgggcatgga caccgccgcc aaggcgatca ttctggaaca 480 gtctggcaag aaccaaggct accgggacgc cgacatccgc agcttctggc ccgagggcgg 540 cgtgtgccta cctggcagcc cagacgtgct ggagtcaggg gtctgcatga aggcagtctg 600 caagcgcgta gctgtggagg gtgtcgacgt gatcttttcc cgagatgcag gcagatacgt 660 ctgtgattat acctattacc tgtctctgca tcatggaaag ggctgcgcgg cactcatcca 720 tgtccctcca ctatcgcgcg ggctcccggc cagcctgctg ggaagagcct tgagaggtca 780 tcatccagca aatgctggaa gagggtgatt gtgaacatct ggtgagagaa tggatgtgaa 840 ggtcttttta gcaacattag aacactacaa aaatcacaca tctgaatgat ttaatggagg 900 gagaaacaga tagcttccct gtcgtcttta ctggcaattt gcatgctgag aaagctcagc 960 tgtcagagaa gaggcaatgc ttttctggag aacgcttcca ggcaacatgc gtgaacacac 1020 gtgccccaca tagctcagct tccctgccac caaagtgtag tgatgcttcc aggagggaca 1080 aaaccaaacc agagacagaa atgcatacag aattatttta tttaacttaa accatgtagt 1140 actttactag aaaaaagcag agtaagagaa actaacgttg ccttagcttc agccattcaa 1200 aatagacagt ttcttttttc cattatgtaa agaatccaga gtatatcgca ataacaggaa 1260 taaattctta caacagaata tacaaaaaca ttttgaaatt tttttcatct actgattttt 1320 tatataaaca ggatttttta ggaataattt atacacagaa agtcatttta tgtaacaaat 1380 tggccatgtt attacctttt tttttcttac ttaaaaaaat ttttttttaa caagaaaact 1440 cagaaaatgc attatttgcg gngcatccat tccatcccgc cttctggttt gatttttttt 1500 atcccagaca aagggatacc cagaggtaga caaactctgg caaaccctnt caccttaacc 1560 tcactgggct taaaaaagca gacagggggt tttcacccgg gcggtctctt ccacccggtg 1620 gatgtg 1626 54 196 PRT Homo Sapiens 54 Met Asp Ser Gln Pro Ser Cys Val Val Val Thr Gly Phe Gly Pro Phe 1 5 10 15 Arg Gln His Leu Val Asn Ser Ser Trp Glu Ala Val Lys Glu Leu Ser 20 25 30 Lys Leu Gly Leu Gly Asn Glu Thr Val Val Gln Leu Arg Thr Leu Glu 35 40 45 Leu Pro Val Asp Tyr Arg Glu Ala Lys Arg Arg Val Thr Gly Ile Trp 50 55 60 Glu Asp His Gln Pro Gln Leu Val Val His Val Gly Met Asp Thr Ala 65 70 75 80 Ala Lys Ala Ile Ile Leu Glu Gln Ser Gly Lys Asn Gln Gly Tyr Arg 85 90 95 Asp Ala Asp Ile Arg Ser Phe Trp Pro Glu Gly Gly Val Cys Leu Pro 100 105 110 Gly Ser Pro Asp Val Leu Glu Ser Gly Val Cys Met Lys Ala Val Cys 115 120 125 Lys Arg Val Ala Val Glu Gly Val Asp Val Ile Phe Ser Arg Asp Ala 130 135 140 Gly Arg Tyr Val Cys Asp Tyr Thr Tyr Tyr Leu Ser Leu His His Gly 145 150 155 160 Lys Gly Cys Ala Ala Leu Ile His Val Pro Pro Leu Ser Arg Gly Leu 165 170 175 Pro Ala Ser Leu Leu Gly Arg Ala Leu Arg Gly His His Pro Ala Asn 180 185 190 Ala Gly Arg Gly 195 55 2335 DNA Homo Sapiens 55 agccatgcgt ctctgagcgc cccgagcgcg cccccgcccc ggaccgtgcc cgggccccgg 60 cgcccccagc ccggcgccgc ccatggccga ggcccccccg cgccgcctcg gcctgggtcc 120 cccgcccggg gacgcccccc gcgcggagct agtggcgctc acggccgtgc agagcgaaca 180 gggcgaggcg ggcgggggcg gctccccgcg ccgcctcggc ctcctgggca gccccctgcc 240 gccgggcgcg cccctccctg ggccgggctc cggctcgggc tccgcctgcg gccagcgctc 300 ctcggccgcg cacaagcgct accgccgcct gcagaactgg gtctacaacg tgctggagcg 360 gccccgcggc tgggccttcg tctaccacgt cttcatattt ttgctggtct tcagctgcct 420 ggtgctgtct gtgctgtcca ctatccagga gcaccaggaa cttgccaacg agtgtctcct 480 catcttggaa ttcgtgatga tcgtggtttt cggcttggag tacatcgtcc gggtctggtc 540 cgccggatgc tgctgccgct accgaggatg gcagggtcgc ttccgctttg ccagaaagcc 600 cttctgtgtc atcgacttca tcgtgttcgt ggcctcggtg gccgtcatcg ccgcgggtac 660 ccagggcaac atcttcgcca cgtccgcgct gcgcagcatg cgcttcctgc agatcctgcg 720 catggtgcgc atggaccgcc gcggcggcac ctggaagctg ctgggctcag tggtctacgc 780 gcatagcaag gagctgatca ccgcctggta catcgggttc ctggtgctca tcttcgcctc 840 cttcctggtc tacctggccg agaaggacgc caactccgac ttctcctcct acgccgactc 900 gctctggtgg gggacgatta cattgacaac catcggctat ggtgacaaga caccgcacac 960 atggctgggc agggtcctgg ctgctggctt cgccttactg ggcatctctt tctttgccct 1020 gcctgccggc atcctaggct ccggctttgc cctgaaggtc caggagcagc accggcagaa 1080 gcacttcgag aagcggagga tgccggcagc caacctcatc caggctgcct ggcgcctgta 1140 ctccaccgat atgagccggg cctacctgac agccacctgg tactactatg acagtatcct 1200 cccatccttc agagagctgg ccctcttgtt tgagcacgtg caacgggccc gcaatggggg 1260 cctacggccc ctggaggtgc ggcgggcgcc ggtacccgac ggagcaccct cccgttaccc 1320 gcccgttgcc acctgccacc ggccgggcag cacctccttc tgccctgggg aaagcagccg 1380 gatgggcatc aaagaccgca tccgcatggg cagctcccag cggcggacgg gtccttccaa 1440 gcagcagctg gcacctccaa caatgcccac ctccccaagc agcgagcagg tgggtgaggc 1500 caccagcccc accaaggtgc aaaagagctg gagcttcaat gaccgcaccc gcttccgggc 1560 atctctgaga ctcaaacccc gcacctctgc tgaggatgcc ccctcagagg aagtagcaga 1620 ggagaagagc taccagtgtg agctcacggt ggacgacatc atgcctgctg tgaagacagt 1680 catccgctcc atcaggattc tcaagttcct ggtggccaaa aggaaattca aggagacact 1740 gcgaccgtac gacgtgaagg acgtcattga gcagtactca gcaggccacc tggacatgct 1800 gggccggatc aagagcctgc aaactcgggt ggaccaaatt gtgggtcggg ggcccgggga 1860 caggaaggcc cgggagaagg gcgacaaggg gccctccgac gcggaggtgg tggatgaaat 1920 cagcatgatg ggacgcgtgg tcaaggtgga gaagcaggtg cagtccatcg agcacaagct 1980 ggacctgctg ttgggcttct attcgcgctg cctgcgctct ggcacctcgg ccagcctggg 2040 cgccgtgcaa gtgccgctgt tcgaccccga catcacctcc gactaccaca gccctgtgga 2100 ccacgaggac atctccgtct ccgcacagac gctcagcatc tcccgctcgg tcagcaccaa 2160 catggactga gggacttctc agaggcaggg cagcacacgg ccagccccgc ggcctggcgc 2220 tccgactgcc ctctgaggcc tccggactcc tctcgtactt gaactcactc cctcacgggg 2280 agagagacca cacgcagtat tgagctgcct gagtgggcgt ggtacctgct gtggg 2335 56 695 PRT Homo Sapiens 56 Met Ala Glu Ala Pro Pro Arg Arg Leu Gly Leu Gly Pro Pro Pro Gly 1 5 10 15 Asp Ala Pro Arg Ala Glu Leu Val Ala Leu Thr Ala Val Gln Ser Glu 20 25 30 Gln Gly Glu Ala Gly Gly Gly Gly Ser Pro Arg Arg Leu Gly Leu Leu 35 40 45 Gly Ser Pro Leu Pro Pro Gly Ala Pro Leu Pro Gly Pro Gly Ser Gly 50 55 60 Ser Gly Ser Ala Cys Gly Gln Arg Ser Ser Ala Ala His Lys Arg Tyr 65 70 75 80 Arg Arg Leu Gln Asn Trp Val Tyr Asn Val Leu Glu Arg Pro Arg Gly 85 90 95 Trp Ala Phe Val Tyr His Val Phe Ile Phe Leu Leu Val Phe Ser Cys 100 105 110 Leu Val Leu Ser Val Leu Ser Thr Ile Gln Glu His Gln Glu Leu Ala 115 120 125 Asn Glu Cys Leu Leu Ile Leu Glu Phe Val Met Ile Val Val Phe Gly 130 135 140 Leu Glu Tyr Ile Val Arg Val Trp Ser Ala Gly Cys Cys Cys Arg Tyr 145 150 155 160 Arg Gly Trp Gln Gly Arg Phe Arg Phe Ala Arg Lys Pro Phe Cys Val 165 170 175 Ile Asp Phe Ile Val Phe Val Ala Ser Val Ala Val Ile Ala Ala Gly 180 185 190 Thr Gln Gly Asn Ile Phe Ala Thr Ser Ala Leu Arg Ser Met Arg Phe 195 200 205 Leu Gln Ile Leu Arg Met Val Arg Met Asp Arg Arg Gly Gly Thr Trp 210 215 220 Lys Leu Leu Gly Ser Val Val Tyr Ala His Ser Lys Glu Leu Ile Thr 225 230 235 240 Ala Trp Tyr Ile Gly Phe Leu Val Leu Ile Phe Ala Ser Phe Leu Val 245 250 255 Tyr Leu Ala Glu Lys Asp Ala Asn Ser Asp Phe Ser Ser Tyr Ala Asp 260 265 270 Ser Leu Trp Trp Gly Thr Ile Thr Leu Thr Thr Ile Gly Tyr Gly Asp 275 280 285 Lys Thr Pro His Thr Trp Leu Gly Arg Val Leu Ala Ala Gly Phe Ala 290 295 300 Leu Leu Gly Ile Ser Phe Phe Ala Leu Pro Ala Gly Ile Leu Gly Ser 305 310 315 320 Gly Phe Ala Leu Lys Val Gln Glu Gln His Arg Gln Lys His Phe Glu 325 330 335 Lys Arg Arg Met Pro Ala Ala Asn Leu Ile Gln Ala Ala Trp Arg Leu 340 345 350 Tyr Ser Thr Asp Met Ser Arg Ala Tyr Leu Thr Ala Thr Trp Tyr Tyr 355 360 365 Tyr Asp Ser Ile Leu Pro Ser Phe Arg Glu Leu Ala Leu Leu Phe Glu 370 375 380 His Val Gln Arg Ala Arg Asn Gly Gly Leu Arg Pro Leu Glu Val Arg 385 390 395 400 Arg Ala Pro Val Pro Asp Gly Ala Pro Ser Arg Tyr Pro Pro Val Ala 405 410 415 Thr Cys His Arg Pro Gly Ser Thr Ser Phe Cys Pro Gly Glu Ser Ser 420 425 430 Arg Met Gly Ile Lys Asp Arg Ile Arg Met Gly Ser Ser Gln Arg Arg 435 440 445 Thr Gly Pro Ser Lys Gln Gln Leu Ala Pro Pro Thr Met Pro Thr Ser 450 455 460 Pro Ser Ser Glu Gln Val Gly Glu Ala Thr Ser Pro Thr Lys Val Gln 465 470 475 480 Lys Ser Trp Ser Phe Asn Asp Arg Thr Arg Phe Arg Ala Ser Leu Arg 485 490 495 Leu Lys Pro Arg Thr Ser Ala Glu Asp Ala Pro Ser Glu Glu Val Ala 500 505 510 Glu Glu Lys Ser Tyr Gln Cys Glu Leu Thr Val Asp Asp Ile Met Pro 515 520 525 Ala Val Lys Thr Val Ile Arg Ser Ile Arg Ile Leu Lys Phe Leu Val 530 535 540 Ala Lys Arg Lys Phe Lys Glu Thr Leu Arg Pro Tyr Asp Val Lys Asp 545 550 555 560 Val Ile Glu Gln Tyr Ser Ala Gly His Leu Asp Met Leu Gly Arg Ile 565 570 575 Lys Ser Leu Gln Thr Arg Val Asp Gln Ile Val Gly Arg Gly Pro Gly 580 585 590 Asp Arg Lys Ala Arg Glu Lys Gly Asp Lys Gly Pro Ser Asp Ala Glu 595 600 605 Val Val Asp Glu Ile Ser Met Met Gly Arg Val Val Lys Val Glu Lys 610 615 620 Gln Val Gln Ser Ile Glu His Lys Leu Asp Leu Leu Leu Gly Phe Tyr 625 630 635 640 Ser Arg Cys Leu Arg Ser Gly Thr Ser Ala Ser Leu Gly Ala Val Gln 645 650 655 Val Pro Leu Phe Asp Pro Asp Ile Thr Ser Asp Tyr His Ser Pro Val 660 665 670 Asp His Glu Asp Ile Ser Val Ser Ala Gln Thr Leu Ser Ile Ser Arg 675 680 685 Ser Val Ser Thr Asn Met Asp 690 695 57 3758 DNA Homo Sapiens 57 cacggagata gacagctttg gagctgctga actccgagca cagggtgaag accccggcgc 60 taccaaccac agcctggcag cctggtctcc gcggcaccca ctggggctgc atccccctcc 120 cccgagaggg ctgcgcaggc gggaagacgc cagaggccag cttcggtccc ccttctgtct 180 ctcggttcct ctttcctccc aagtaaggga ataaaccgcg aagaaggagc gccccgggcc 240 accgcgcaac caagtgttgc ctggtgagga agagccagga cttctgaatt taccttgaat 300 acagacagga ggatgttgcc taaggaatag cagagatctt gtctcatctt ctgagaggtg 360 cctgctgctg ctgtatacac ttgagtgctc ccagaagtct cctgaaaggc ttacatcgca 420 aacctgcaat gagccaggcc ctgggctggg cctccacttc agcctagtga acaaaactcc 480 atcactgccc tttagccact cacataaagt ttaaaaatgg gtgaagaacg gtgggtctcc 540 ctcactccag aagaatttga ccaactccag aaatattcag aatattcctc caagaagata 600 aaagatgcct tgactgaatt taatgagggt gggagcctca aacaatatga cccacatgag 660 ccgattagct atgatgtctt caagctgttc atgagggcgt acctggaggt ggaccttccc 720 cagccactga gcactcacct cttcctggcc ttcagccaga agcccagaca cgagacctct 780 gaccacccga cggagggagc cagcaacagt gaggccaaca gcgcagatac taatatacag 840 aatgcagata atgccaccaa agcagacgag gcctgtgccc ctgatactga atcaaatatg 900 gctgagaagc aagcaccagc tgaagaccaa gtggctgcga cccccctgga accccccgtc 960 cctcggtctt caagctcgga atccccagtg gtgtacctga aggatgttgt gtgctacctg 1020 tccctgctgg agacggggag gcctcaggat aagctggagt tcatgtttcg cctctatgat 1080 tcagatgaga acggtctcct ggaccaagcg gagatggatt gcattgtcaa ccaaatgctg 1140 catattgccc agtacctgga gtgggatccc acagagctga ggcctatatt gaaggagatg 1200 ctgcaaggga tggactacga ccgggacggc tttgtgtctc tacaggaatg ggtccatgga 1260 gggatgacca ccatcccatt gctggtgctc ctggggatgg atgactctgg ctccaagggg 1320 gatggggggc acgcctggac catgaagcac ttcaagaaac caacctactg caacttctgc 1380 catatcatgc tcatgggcgt ccgcaagcaa ggcctgtgct gcacttactg taaatacact 1440 gtccacgaac gctgtgtgtc caaaaacatt cctggttgtg tcaaaacgta ctcaaaagcc 1500 aaaaggagtg gtgaggtgat gcagcacgca tgggtggaag ggaactcctc cgtcaagtgt 1560 gaccggtgcc acaaaagtat caagtgctac cagagtgtca ccgcgcggca ctgcgtgtgg 1620 tgccggatga cgtttcaccg caaatgtgaa ttatcaacgt tgtgtgacgg tggggaactc 1680 agagaccaca tcttactgcc cacctccata tgccccatca cccgggacag gccaggtgag 1740 aagtctgatg gctgcgtgtc cgccaagggc gaacttgtca tgcagtataa gatcatcccc 1800 accccgggta cccaccccct gctggtcttg gtgaacccca agagtggagg gagacaagga 1860 gaaagaattc ttcggaaatt ccactatctg ctcaacccca aacaagtttt caacctggac 1920 aatggggggc ctactccagg gttgaacttt ttccgtgata ctccagactt ccgtgttttg 1980 gcctgtggtg gagatgggac agttggctgg attttggatt gcattgataa ggccaacttt 2040 gcaaagcatc caccagtggc tgtcctgcct cttggaacag gaaatgacct tgcccgttgt 2100 ctccgctggg gaggaggtta tgaagggggc agcttgacaa aaatcctgaa agacattgag 2160 cagagcccct tggtgatgct ggaccgctgg catctggaag tcatccccag agaggaagtg 2220 gaaaacgggg accaggtccc atacagcatc atgaacaact atttctccat tggtgtggac 2280 gcttccattg cacacagatt ccatgtgatg agagagaaac atcctgaaaa attcaacagc 2340 aggatgaaga acaagctgtg gtactttgaa tttggcacct cggagacttt tgcagcgacc 2400 tgcaagaaac tccacgacca cattgagttg gagtgtgatg gggttggggt ggacctgagc 2460 aacatcttcc tggaaggcat tgccattctc aacattccca gcatgtacgg aggcaccaat 2520 ctctggggag aaaacaagaa gaaccgggct gtgatccggg aaagcaggaa gggtgtcact 2580 gaccccaaag aactgaaatt ctgcgttcaa gacctcagtg accagctcct tgaagtggtg 2640 gggctagaag gagccatgga gatggggcag atctacaccg gcctgaagag tgcaggcagg 2700 aggctggccc agtgcgcctc tgtcaccatc aggacaaaca agctgctgcc aatgcaagtg 2760 gatggagaac cctggatgca gccatgttgc acgattaaaa ttactcacaa gaaccaagcg 2820 cccatgatga tggggcctcc ccagaagagc agcttcttct cgttgagaag gaagagccgt 2880 tcaaaagact aaacagtgtg ccaaacacca gctaaaccaa gagagaaagc aagaaactat 2940 aatgcacact cacacacaat ttatgtgcac actcacacat gcacacacac acacacatac 3000 acactcttct ctaaccagtg gaagcaaagc cacccttcgg gaagaaaacg tcaccttgcc 3060 atacattctg tttcaacagt gggtacaccc ctaacagagc cagtgccaac aaaacatttt 3120 gaatggactt agggcccatg aggttgtggc tggcttaggc agcaacctcc acattcccac 3180 aggccttgag cagaattttc tgagactgaa gggaaatccc cctttctttc taccagccct 3240 gcaagtttcc tcatggacgc tcgcgaggag caggctgcag gtttcctgcc tatggtgaga 3300 tcagatgtgg ccaagggaag gagctctggt tccagagaat ttgcacaaag ttccctctgt 3360 acagagacaa aacggcctcc ggctctcaga gcataatcct tggcagggct cagcaggcgc 3420 acgttggttt cttggtcgtc ctttgagtga caacttctcc gtgaacctgc tgaagaggca 3480 gaaaggctgt ggaaagctgt atttccattc ttgggtttct gcgccgtcgg tgggcacttg 3540 ttattttcca ggaaccttct cctggtgtct acatgtttgc ttagaggcgg ctccaagagc 3600 cccagagctg cctgcatagc acaccttaga tgtggtattt attttcttag ttctgtgaac 3660 acctgggagg gagagcggag aaactgggat ttatttttca aattggtgtc ataatattgt 3720 gtaaaaaggg aaggaaaaaa aaaaccaccc ccagcttc 3758 58 791 PRT Homo Sapiens 58 Met Gly Glu Glu Arg Trp Val Ser Leu Thr Pro Glu Glu Phe Asp Gln 1 5 10 15 Leu Gln Lys Tyr Ser Glu Tyr Ser Ser Lys Lys Ile Lys Asp Ala Leu 20 25 30 Thr Glu Phe Asn Glu Gly Gly Ser Leu Lys Gln Tyr Asp Pro His Glu 35 40 45 Pro Ile Ser Tyr Asp Val Phe Lys Leu Phe Met Arg Ala Tyr Leu Glu 50 55 60 Val Asp Leu Pro Gln Pro Leu Ser Thr His Leu Phe Leu Ala Phe Ser 65 70 75 80 Gln Lys Pro Arg His Glu Thr Ser Asp His Pro Thr Glu Gly Ala Ser 85 90 95 Asn Ser Glu Ala Asn Ser Ala Asp Thr Asn Ile Gln Asn Ala Asp Asn 100 105 110 Ala Thr Lys Ala Asp Glu Ala Cys Ala Pro Asp Thr Glu Ser Asn Met 115 120 125 Ala Glu Lys Gln Ala Pro Ala Glu Asp Gln Val Ala Ala Thr Pro Leu 130 135 140 Glu Pro Pro Val Pro Arg Ser Ser Ser Ser Glu Ser Pro Val Val Tyr 145 150 155 160 Leu Lys Asp Val Val Cys Tyr Leu Ser Leu Leu Glu Thr Gly Arg Pro 165 170 175 Gln Asp Lys Leu Glu Phe Met Phe Arg Leu Tyr Asp Ser Asp Glu Asn 180 185 190 Gly Leu Leu Asp Gln Ala Glu Met Asp Cys Ile Val Asn Gln Met Leu 195 200 205 His Ile Ala Gln Tyr Leu Glu Trp Asp Pro Thr Glu Leu Arg Pro Ile 210 215 220 Leu Lys Glu Met Leu Gln Gly Met Asp Tyr Asp Arg Asp Gly Phe Val 225 230 235 240 Ser Leu Gln Glu Trp Val His Gly Gly Met Thr Thr Ile Pro Leu Leu 245 250 255 Val Leu Leu Gly Met Asp Asp Ser Gly Ser Lys Gly Asp Gly Gly His 260 265 270 Ala Trp Thr Met Lys His Phe Lys Lys Pro Thr Tyr Cys Asn Phe Cys 275 280 285 His Ile Met Leu Met Gly Val Arg Lys Gln Gly Leu Cys Cys Thr Tyr 290 295 300 Cys Lys Tyr Thr Val His Glu Arg Cys Val Ser Lys Asn Ile Pro Gly 305 310 315 320 Cys Val Lys Thr Tyr Ser Lys Ala Lys Arg Ser Gly Glu Val Met Gln 325 330 335 His Ala Trp Val Glu Gly Asn Ser Ser Val Lys Cys Asp Arg Cys His 340 345 350 Lys Ser Ile Lys Cys Tyr Gln Ser Val Thr Ala Arg His Cys Val Trp 355 360 365 Cys Arg Met Thr Phe His Arg Lys Cys Glu Leu Ser Thr Leu Cys Asp 370 375 380 Gly Gly Glu Leu Arg Asp His Ile Leu Leu Pro Thr Ser Ile Cys Pro 385 390 395 400 Ile Thr Arg Asp Arg Pro Gly Glu Lys Ser Asp Gly Cys Val Ser Ala 405 410 415 Lys Gly Glu Leu Val Met Gln Tyr Lys Ile Ile Pro Thr Pro Gly Thr 420 425 430 His Pro Leu Leu Val Leu Val Asn Pro Lys Ser Gly Gly Arg Gln Gly 435 440 445 Glu Arg Ile Leu Arg Lys Phe His Tyr Leu Leu Asn Pro Lys Gln Val 450 455 460 Phe Asn Leu Asp Asn Gly Gly Pro Thr Pro Gly Leu Asn Phe Phe Arg 465 470 475 480 Asp Thr Pro Asp Phe Arg Val Leu Ala Cys Gly Gly Asp Gly Thr Val 485 490 495 Gly Trp Ile Leu Asp Cys Ile Asp Lys Ala Asn Phe Ala Lys His Pro 500 505 510 Pro Val Ala Val Leu Pro Leu Gly Thr Gly Asn Asp Leu Ala Arg Cys 515 520 525 Leu Arg Trp Gly Gly Gly Tyr Glu Gly Gly Ser Leu Thr Lys Ile Leu 530 535 540 Lys Asp Ile Glu Gln Ser Pro Leu Val Met Leu Asp Arg Trp His Leu 545 550 555 560 Glu Val Ile Pro Arg Glu Glu Val Glu Asn Gly Asp Gln Val Pro Tyr 565 570 575 Ser Ile Met Asn Asn Tyr Phe Ser Ile Gly Val Asp Ala Ser Ile Ala 580 585 590 His Arg Phe His Val Met Arg Glu Lys His Pro Glu Lys Phe Asn Ser 595 600 605 Arg Met Lys Asn Lys Leu Trp Tyr Phe Glu Phe Gly Thr Ser Glu Thr 610 615 620 Phe Ala Ala Thr Cys Lys Lys Leu His Asp His Ile Glu Leu Glu Cys 625 630 635 640 Asp Gly Val Gly Val Asp Leu Ser Asn Ile Phe Leu Glu Gly Ile Ala 645 650 655 Ile Leu Asn Ile Pro Ser Met Tyr Gly Gly Thr Asn Leu Trp Gly Glu 660 665 670 Asn Lys Lys Asn Arg Ala Val Ile Arg Glu Ser Arg Lys Gly Val Thr 675 680 685 Asp Pro Lys Glu Leu Lys Phe Cys Val Gln Asp Leu Ser Asp Gln Leu 690 695 700 Leu Glu Val Val Gly Leu Glu Gly Ala Met Glu Met Gly Gln Ile Tyr 705 710 715 720 Thr Gly Leu Lys Ser Ala Gly Arg Arg Leu Ala Gln Cys Ala Ser Val 725 730 735 Thr Ile Arg Thr Asn Lys Leu Leu Pro Met Gln Val Asp Gly Glu Pro 740 745 750 Trp Met Gln Pro Cys Cys Thr Ile Lys Ile Thr His Lys Asn Gln Ala 755 760 765 Pro Met Met Met Gly Pro Pro Gln Lys Ser Ser Phe Phe Ser Leu Arg 770 775 780 Arg Lys Ser Arg Ser Lys Asp 785 790 59 1270 DNA Homo Sapiens 59 ggagagggtg tgagggcaga tctgggggtg cccagatgga aggaggcagg catgggggac 60 acccaaggcc ccctggcagc accatgaact aagcaggaca cctggagggg aagaactgtg 120 gggacctgga ggcctccaac gactccttcc tgcttcctgg acaggactat ggctgtgcag 180 ggatcccaga gaagacttct gggctccctc aactccaccc ccacagccat cccccagctg 240 gggctggctg ccaaccagac aggagcccgg tgcctggagg tgtccatctc tgacgggctc 300 ttcctcagcc tggggctggt gagcttggtg gagaacgcgc tggtggtggc caccatcgcc 360 aagaaccgga acctgcactc acccatgtac tgcttcatct gctgcctggc cttgtcggac 420 ctgctggtga gcgggagcaa cgtgctggag acggccgtca tcctcctgct ggaggccggt 480 gcactggtgg cccgggctgc ggtgctgcag cagctggaca atgtcattga cgtgatcacc 540 tgcagctcca tgctgtccag cctctgcttc ctgggcgcca tcgccgtgga ccgctacatc 600 tccatcttct acgcactgcg ctaccacagc atcgtgaccc tgccgcgggc gcggcaagcc 660 gttgcggcca tctgggtggc cagtgtcgtc ttcagcacgc tcttcatcgc ctactacgac 720 cacgtggccg tcctgctgtg cctcgtggtc ttcttcctgg ctatgctggt gctcatggcc 780 gtgctgtacg tccacatgct ggcccgggcc tgccagcacg cccagggcat cgcccggctc 840 cacaagaggc agcgcccggt ccaccagggc tttggcctta aaggcgctgt caccctcacc 900 atcctgctgg gcattttctt cctctgctgg ggccccttct tcctgcatct cacactcatc 960 gtcctctgcc ccgagcaccc cacgtgcggc tgcatcttca agaacttcaa cctctttctc 1020 gccctcatca tctgcaatgc catcatcgac cccctcatct acgccttcca cagccaggag 1080 ctccgcagga cgctcaagga ggtgctgaca tgctcctggt gagcgcggtg cacgcgcttt 1140 aagtgtgctg ggcagaggga ggtggtgata ttgtgtggtc tggttcctgt gtgaccctgg 1200 gcagttcctt acctccctgg tccccgtttg tcaaagagga tggactaaat gatctctgaa 1260 agtgttgaag 1270 60 317 PRT Homo Sapiens 60 Met Ala Val Gln Gly Ser Gln Arg Arg Leu Leu Gly Ser Leu Asn Ser 1 5 10 15 Thr Pro Thr Ala Ile Pro Gln Leu Gly Leu Ala Ala Asn Gln Thr Gly 20 25 30 Ala Arg Cys Leu Glu Val Ser Ile Ser Asp Gly Leu Phe Leu Ser Leu 35 40 45 Gly Leu Val Ser Leu Val Glu Asn Ala Leu Val Val Ala Thr Ile Ala 50 55 60 Lys Asn Arg Asn Leu His Ser Pro Met Tyr Cys Phe Ile Cys Cys Leu 65 70 75 80 Ala Leu Ser Asp Leu Leu Val Ser Gly Ser Asn Val Leu Glu Thr Ala 85 90 95 Val Ile Leu Leu Leu Glu Ala Gly Ala Leu Val Ala Arg Ala Ala Val 100 105 110 Leu Gln Gln Leu Asp Asn Val Ile Asp Val Ile Thr Cys Ser Ser Met 115 120 125 Leu Ser Ser Leu Cys Phe Leu Gly Ala Ile Ala Val Asp Arg Tyr Ile 130 135 140 Ser Ile Phe Tyr Ala Leu Arg Tyr His Ser Ile Val Thr Leu Pro Arg 145 150 155 160 Ala Arg Gln Ala Val Ala Ala Ile Trp Val Ala Ser Val Val Phe Ser 165 170 175 Thr Leu Phe Ile Ala Tyr Tyr Asp His Val Ala Val Leu Leu Cys Leu 180 185 190 Val Val Phe Phe Leu Ala Met Leu Val Leu Met Ala Val Leu Tyr Val 195 200 205 His Met Leu Ala Arg Ala Cys Gln His Ala Gln Gly Ile Ala Arg Leu 210 215 220 His Lys Arg Gln Arg Pro Val His Gln Gly Phe Gly Leu Lys Gly Ala 225 230 235 240 Val Thr Leu Thr Ile Leu Leu Gly Ile Phe Phe Leu Cys Trp Gly Pro 245 250 255 Phe Phe Leu His Leu Thr Leu Ile Val Leu Cys Pro Glu His Pro Thr 260 265 270 Cys Gly Cys Ile Phe Lys Asn Phe Asn Leu Phe Leu Ala Leu Ile Ile 275 280 285 Cys Asn Ala Ile Ile Asp Pro Leu Ile Tyr Ala Phe His Ser Gln Glu 290 295 300 Leu Arg Arg Thr Leu Lys Glu Val Leu Thr Cys Ser Trp 305 310 315 61 1599 DNA Homo Sapiens 61 cgaaccagtg caatgacgat gccagtcaac ggggcccaca aggatgctga cctgtggtcc 60 tcacatgaca agatgctggc acaacccctc aaagacagtg atgttgaggt ttacaacatc 120 attaagaagg agagtaaccg gcagagggtt ggattggagc tgattgcctc ggagaatttc 180 gccagccgag cagttttgga ggccctaggc tcttgcttaa ataacaaata ctctgagggg 240 tacccgggcc agagatacta tggcgggact gagtttattg atgaactgga gaccctctgt 300 cagaagcgag ccctgcaggc ctataagctg gacccacagt gctggggggt caacgtccag 360 ccctactcag gctcccctgc aaactttgct gtgtacactg ccctggtgga accccatggg 420 cgcatcatgg gcctggacct tccggatggg ggccacctga cccatgggtt catgacagac 480 aagaagaaaa tctctgccac gtccatcttc tttgaatcta tgccctacaa ggtgaaccca 540 gatactggct acatcaacta tgaccagctg gaggagaacg cacgcctctt ccacccgaag 600 ctgatcatcg caggaaccag ctgctactcc cgaaacctgg aatatgcccg gctacggaag 660 attgcagatg agaacggggc gtatctcatg gcggacatgg ctcacatcag cgggctggtg 720 gcggctggcg tggtgccctc cccatttgaa cactgccatg tggtgaccac caccactcac 780 aagaccctgc gaggctgccg agctggcatg atcttctaca ggaaaggagt gaaaagtgtg 840 gatcccaaga ctggcaaaga gattctgtac aacctggagt ctcttatcaa ttctgctgtg 900 ttccctggcc tgcagggagg tccccacaac cacgccattg ctggggttgc tgtggcactg 960 aagcaagcta tgactctgga atttaaagtt tatcaacacc aggtggtggc caactgcagg 1020 gctctgtctg aggccctgac ggagctgggc tacaaaatag tcacaggtgg ttctgacaac 1080 catttgatcc ttgtggatct ccgttccaaa ggcacagatg gtggaagggc tgagaaggtg 1140 ctagaagcct gttctattgc ctgcaacaag aacacctgtc caggtgacag aagcgctctg 1200 cggcccagtg gactgcggct ggggacccca gcactgacgt cccgtggact tttggaaaaa 1260 gacttccaaa aagtagccca ctttattcac agagggatag agctgaccct gcagatccag 1320 agcgacactg gtgtcagagc caccctgaaa gagttcaagg agagactggc aggggataag 1380 taccaggcgg ccgtgcaggc tctccgggag gaggttgaga gcttcgcctc tctcttccct 1440 ctgcctggcc tgcctgactt ctaaaggagc gggcccactc tggacccacc tggcgccaca 1500 gaggaagctg cctgccggag gacccccacc tgagagatgg atgagctgct ccaaaggggg 1560 actgttgaca ctcgggccct ttgagggggt ttcttttgg 1599 62 483 PRT Homo Sapiens 62 Met Thr Met Pro Val Asn Gly Ala His Lys Asp Ala Asp Leu Trp Ser 1 5 10 15 Ser His Asp Lys Met Leu Ala Gln Pro Leu Lys Asp Ser Asp Val Glu 20 25 30 Val Tyr Asn Ile Ile Lys Lys Glu Ser Asn Arg Gln Arg Val Gly Leu 35 40 45 Glu Leu Ile Ala Ser Glu Asn Phe Ala Ser Arg Ala Val Leu Glu Ala 50 55 60 Leu Gly Ser Cys Leu Asn Asn Lys Tyr Ser Glu Gly Tyr Pro Gly Gln 65 70 75 80 Arg Tyr Tyr Gly Gly Thr Glu Phe Ile Asp Glu Leu Glu Thr Leu Cys 85 90 95 Gln Lys Arg Ala Leu Gln Ala Tyr Lys Leu Asp Pro Gln Cys Trp Gly 100 105 110 Val Asn Val Gln Pro Tyr Ser Gly Ser Pro Ala Asn Phe Ala Val Tyr 115 120 125 Thr Ala Leu Val Glu Pro His Gly Arg Ile Met Gly Leu Asp Leu Pro 130 135 140 Asp Gly Gly His Leu Thr His Gly Phe Met Thr Asp Lys Lys Lys Ile 145 150 155 160 Ser Ala Thr Ser Ile Phe Phe Glu Ser Met Pro Tyr Lys Val Asn Pro 165 170 175 Asp Thr Gly Tyr Ile Asn Tyr Asp Gln Leu Glu Glu Asn Ala Arg Leu 180 185 190 Phe His Pro Lys Leu Ile Ile Ala Gly Thr Ser Cys Tyr Ser Arg Asn 195 200 205 Leu Glu Tyr Ala Arg Leu Arg Lys Ile Ala Asp Glu Asn Gly Ala Tyr 210 215 220 Leu Met Ala Asp Met Ala His Ile Ser Gly Leu Val Ala Ala Gly Val 225 230 235 240 Val Pro Ser Pro Phe Glu His Cys His Val Val Thr Thr Thr Thr His 245 250 255 Lys Thr Leu Arg Gly Cys Arg Ala Gly Met Ile Phe Tyr Arg Lys Gly 260 265 270 Val Lys Ser Val Asp Pro Lys Thr Gly Lys Glu Ile Leu Tyr Asn Leu 275 280 285 Glu Ser Leu Ile Asn Ser Ala Val Phe Pro Gly Leu Gln Gly Gly Pro 290 295 300 His Asn His Ala Ile Ala Gly Val Ala Val Ala Leu Lys Gln Ala Met 305 310 315 320 Thr Leu Glu Phe Lys Val Tyr Gln His Gln Val Val Ala Asn Cys Arg 325 330 335 Ala Leu Ser Glu Ala Leu Thr Glu Leu Gly Tyr Lys Ile Val Thr Gly 340 345 350 Gly Ser Asp Asn His Leu Ile Leu Val Asp Leu Arg Ser Lys Gly Thr 355 360 365 Asp Gly Gly Arg Ala Glu Lys Val Leu Glu Ala Cys Ser Ile Ala Cys 370 375 380 Asn Lys Asn Thr Cys Pro Gly Asp Arg Ser Ala Leu Arg Pro Ser Gly 385 390 395 400 Leu Arg Leu Gly Thr Pro Ala Leu Thr Ser Arg Gly Leu Leu Glu Lys 405 410 415 Asp Phe Gln Lys Val Ala His Phe Ile His Arg Gly Ile Glu Leu Thr 420 425 430 Leu Gln Ile Gln Ser Asp Thr Gly Val Arg Ala Thr Leu Lys Glu Phe 435 440 445 Lys Glu Arg Leu Ala Gly Asp Lys Tyr Gln Ala Ala Val Gln Ala Leu 450 455 460 Arg Glu Glu Val Glu Ser Phe Ala Ser Leu Phe Pro Leu Pro Gly Leu 465 470 475 480 Pro Asp Phe 63 1791 DNA Homo Sapiens 63 ggcggacgga gcgagccctg ggcgagtgaa ttgtggctgt gggttgacgg tggagacacc 60 ccccggagag gcggagggaa gggaggcgag gctgcacctg catgcttccc gcctcccact 120 ccccagcgcc cccggaccgt gcagttctct gcaggaccag gccatggagc tcgaagtccg 180 gcgggtccga caggcgttcc tgtccggccg gtcgcgacct ctgcggtttc ggctgcagca 240 gctggaggcc ctgcggagga tggtgcagga gcgcgagaag gatatcctga cggccatcgc 300 cgccgacctg tgcaagagtg aattcaatgt gtacagtcag gaagtcatta ctgtccttgg 360 ggaaattgat tttatgcttg agaatcttcc tgaatgggtt actgctaaac cagttaagaa 420 gaacgtgctc accatgctgg atgaggccta tattcagcca cagcctctgg gagtggtgct 480 gataatcgga gcttggaatt accccttcgt tctcaccatt cagccactga taggagccat 540 cgctgcagga aatgctgtga ttataaagcc ttctgaactg agtgaaaata cagccaagat 600 cttggcaaag cttctccctc agtatttaga ccaggatctc tatattgtta ttaatggtgg 660 tgttgaggaa accacggagc tcctgaagca gcgatttgac cacattttct atacgggaaa 720 cactgcggtt ggcaaaattg tcatggaagc tgctgccaag catctgaccc ctgtgactct 780 tgaactggga gggaaaagtc catgttatat tgataaagat tgtgacctgg acattgtttg 840 cagacgcata acctggggaa aatacatgaa ttgtggccaa acctgcattg cacccgacta 900 tattctctgt gaagcatccc tccaaaatca aattgtatgg aagattaagg aaacagtgaa 960 ggaattttat ggagaaaata taaaagagtc tcctgattat gaaaggatca tcaatcttcg 1020 tcattttaag aggatactaa gtttgcttga aggacaaaag atagcttttg gtggggagac 1080 tgatgaggcc acacgctaca tagccccaac agtacttacc gatgttgatc ctaaaaccaa 1140 ggtgatgcaa gaagaaattt ttggaccaat tcttccaata gtgcctgtga aaaatgtaga 1200 tgaggccata aatttcataa atgaacgtga aaagcctctg gctctttatg tattttcgca 1260 taaccataag ctcatcaaac ggatgattga tgagacatcc agtggaggtg tcacaggcaa 1320 tgacgtcatt atgcacttca cgctcaactc tttcccattt ggaggagtgg gttccagtgg 1380 gatgggagct tatcacggaa aacatagttt tgatactttt tctcatcagc gtccctgttt 1440 attaaaaagt ttaaagagag aaggtgctaa caaactcaga tatcctccca acagccagtc 1500 aaaggtggat tgggggaaat tttttctctt gaaacggttc aacaaagaaa aactcggtct 1560 cctgttgctc actttcctgg gtattgtagc cgctgtgctt gtcaaggcag aatattactg 1620 aagaatgatc ctgttcaacc tcctagtgcc tctactgaat tattcctctt ttaaatggtt 1680 aatgaaccaa taatttttaa atcataccaa aaatagtaag aaaatatgca aacactctgt 1740 gatcaaactt aaaagtcatt gccattcatc attaataaaa gttgccattt c 1791 64 485 PRT Homo Sapiens 64 Met Glu Leu Glu Val Arg Arg Val Arg Gln Ala Phe Leu Ser Gly Arg 1 5 10 15 Ser Arg Pro Leu Arg Phe Arg Leu Gln Gln Leu Glu Ala Leu Arg Arg 20 25 30 Met Val Gln Glu Arg Glu Lys Asp Ile Leu Thr Ala Ile Ala Ala Asp 35 40 45 Leu Cys Lys Ser Glu Phe Asn Val Tyr Ser Gln Glu Val Ile Thr Val 50 55 60 Leu Gly Glu Ile Asp Phe Met Leu Glu Asn Leu Pro Glu Trp Val Thr 65 70 75 80 Ala Lys Pro Val Lys Lys Asn Val Leu Thr Met Leu Asp Glu Ala Tyr 85 90 95 Ile Gln Pro Gln Pro Leu Gly Val Val Leu Ile Ile Gly Ala Trp Asn 100 105 110 Tyr Pro Phe Val Leu Thr Ile Gln Pro Leu Ile Gly Ala Ile Ala Ala 115 120 125 Gly Asn Ala Val Ile Ile Lys Pro Ser Glu Leu Ser Glu Asn Thr Ala 130 135 140 Lys Ile Leu Ala Lys Leu Leu Pro Gln Tyr Leu Asp Gln Asp Leu Tyr 145 150 155 160 Ile Val Ile Asn Gly Gly Val Glu Glu Thr Thr Glu Leu Leu Lys Gln 165 170 175 Arg Phe Asp His Ile Phe Tyr Thr Gly Asn Thr Ala Val Gly Lys Ile 180 185 190 Val Met Glu Ala Ala Ala Lys His Leu Thr Pro Val Thr Leu Glu Leu 195 200 205 Gly Gly Lys Ser Pro Cys Tyr Ile Asp Lys Asp Cys Asp Leu Asp Ile 210 215 220 Val Cys Arg Arg Ile Thr Trp Gly Lys Tyr Met Asn Cys Gly Gln Thr 225 230 235 240 Cys Ile Ala Pro Asp Tyr Ile Leu Cys Glu Ala Ser Leu Gln Asn Gln 245 250 255 Ile Val Trp Lys Ile Lys Glu Thr Val Lys Glu Phe Tyr Gly Glu Asn 260 265 270 Ile Lys Glu Ser Pro Asp Tyr Glu Arg Ile Ile Asn Leu Arg His Phe 275 280 285 Lys Arg Ile Leu Ser Leu Leu Glu Gly Gln Lys Ile Ala Phe Gly Gly 290 295 300 Glu Thr Asp Glu Ala Thr Arg Tyr Ile Ala Pro Thr Val Leu Thr Asp 305 310 315 320 Val Asp Pro Lys Thr Lys Val Met Gln Glu Glu Ile Phe Gly Pro Ile 325 330 335 Leu Pro Ile Val Pro Val Lys Asn Val Asp Glu Ala Ile Asn Phe Ile 340 345 350 Asn Glu Arg Glu Lys Pro Leu Ala Leu Tyr Val Phe Ser His Asn His 355 360 365 Lys Leu Ile Lys Arg Met Ile Asp Glu Thr Ser Ser Gly Gly Val Thr 370 375 380 Gly Asn Asp Val Ile Met His Phe Thr Leu Asn Ser Phe Pro Phe Gly 385 390 395 400 Gly Val Gly Ser Ser Gly Met Gly Ala Tyr His Gly Lys His Ser Phe 405 410 415 Asp Thr Phe Ser His Gln Arg Pro Cys Leu Leu Lys Ser Leu Lys Arg 420 425 430 Glu Gly Ala Asn Lys Leu Arg Tyr Pro Pro Asn Ser Gln Ser Lys Val 435 440 445 Asp Trp Gly Lys Phe Phe Leu Leu Lys Arg Phe Asn Lys Glu Lys Leu 450 455 460 Gly Leu Leu Leu Leu Thr Phe Leu Gly Ile Val Ala Ala Val Leu Val 465 470 475 480 Lys Ala Glu Tyr Tyr 485 65 1487 DNA Homo Sapiens 65 gcggcaggtt gggtgcggac catggcctct cacaagctgc tggtgacccc ccccaaggcc 60 ctgctcaagc ccctctccat ccccaaccag ctcctgctgg ggcctggtcc ttccaacctg 120 cctcctcgca tcatggcagc cggggggctg cagatgatcg ggtccatgag caaggatatg 180 taccagatca tggacgagat caaggaaggc atccagtacg tgttccagac caggaaccca 240 ctcacactgg tcatctctgg ctcgggacac tgtgccctgg aggccgccct ggtcaatgtg 300 ctggagcctg gggactcctt cctggttggg gccaatggca tttgggggca gcgagccgtg 360 gacatcgggg agcgcatagg agcccgagtg cacccgatga ccaaggaccc tggaggccac 420 tacacactgc aggaggtgga ggagggcctg gcccagcaca agccagtgct gctgttctta 480 acccacgggg agtcgtccac cggcgtgctg cagccccttg atggcttcgg ggaactctgc 540 cacaggtaca agtgcctgct cctggtggat tcggtggcat ccctgggcgg gacccccctt 600 tacatggacc ggcaaggcat cgacatcctg tactcgggct cccagaaggc cctgaacgcc 660 cctccaggga cctcgctcat ctccttcagt gacaaggcca aaaagaagat gtactcccgc 720 aagacgaagc ccttctcctt ctacctggac atcaagtggc tggccaactt ctggggctgt 780 gacgaccagc ccaggatgta ccatcacaca atccccgtca tcagcctgta cagcctgaga 840 gagagcctgg ccctcattgc ggaacagggc ctggagaaca gctggcgcca gcaccgcgag 900 gccgcggcgt atctgcatgg gcgcctgcag gcactggggc tgcagctctt cgtgaaggac 960 ccggcgctcc ggcttcccac agtcaccact gtggctgtac ccgctggcta tgactggaga 1020 gacatcgtca gctacgtcat agaccacttc gacattgaga tcatgggtgg ccttgggccc 1080 tccacgggga aggtgctgcg gatcggcctg ctgggctgca atgccacccg cgagaatgtg 1140 gaccgcgtga cggaggccct gagggcggcc ctgcagcact gccccaagaa gaagctgtga 1200 cctgcccact ggcacacagc tggcactggc acacacctgt cccatgccca ccctgaggga 1260 tcaggagcaa acagaccctg caaggtcctc caggcctggg gacaggaaag ccactgaccc 1320 agcccgggag gcagaaccag gcagcctccc tggccccagg cagccctttt ccctccagtg 1380 gcacctcctg gaaacagtcc acttgggcgc aaaacccagt gccttccaaa tgagctgcag 1440 tccccaggcc atgagcctcc cgggaatgtt taataaaggg cctggcc 1487 66 392 PRT Homo Sapiens 66 Met Ala Ser His Lys Leu Leu Val Thr Pro Pro Lys Ala Leu Leu Lys 1 5 10 15 Pro Leu Ser Ile Pro Asn Gln Leu Leu Leu Gly Pro Gly Pro Ser Asn 20 25 30 Leu Pro Pro Arg Ile Met Ala Ala Gly Gly Leu Gln Met Ile Gly Ser 35 40 45 Met Ser Lys Asp Met Tyr Gln Ile Met Asp Glu Ile Lys Glu Gly Ile 50 55 60 Gln Tyr Val Phe Gln Thr Arg Asn Pro Leu Thr Leu Val Ile Ser Gly 65 70 75 80 Ser Gly His Cys Ala Leu Glu Ala Ala Leu Val Asn Val Leu Glu Pro 85 90 95 Gly Asp Ser Phe Leu Val Gly Ala Asn Gly Ile Trp Gly Gln Arg Ala 100 105 110 Val Asp Ile Gly Glu Arg Ile Gly Ala Arg Val His Pro Met Thr Lys 115 120 125 Asp Pro Gly Gly His Tyr Thr Leu Gln Glu Val Glu Glu Gly Leu Ala 130 135 140 Gln His Lys Pro Val Leu Leu Phe Leu Thr His Gly Glu Ser Ser Thr 145 150 155 160 Gly Val Leu Gln Pro Leu Asp Gly Phe Gly Glu Leu Cys His Arg Tyr 165 170 175 Lys Cys Leu Leu Leu Val Asp Ser Val Ala Ser Leu Gly Gly Thr Pro 180 185 190 Leu Tyr Met Asp Arg Gln Gly Ile Asp Ile Leu Tyr Ser Gly Ser Gln 195 200 205 Lys Ala Leu Asn Ala Pro Pro Gly Thr Ser Leu Ile Ser Phe Ser Asp 210 215 220 Lys Ala Lys Lys Lys Met Tyr Ser Arg Lys Thr Lys Pro Phe Ser Phe 225 230 235 240 Tyr Leu Asp Ile Lys Trp Leu Ala Asn Phe Trp Gly Cys Asp Asp Gln 245 250 255 Pro Arg Met Tyr His His Thr Ile Pro Val Ile Ser Leu Tyr Ser Leu 260 265 270 Arg Glu Ser Leu Ala Leu Ile Ala Glu Gln Gly Leu Glu Asn Ser Trp 275 280 285 Arg Gln His Arg Glu Ala Ala Ala Tyr Leu His Gly Arg Leu Gln Ala 290 295 300 Leu Gly Leu Gln Leu Phe Val Lys Asp Pro Ala Leu Arg Leu Pro Thr 305 310 315 320 Val Thr Thr Val Ala Val Pro Ala Gly Tyr Asp Trp Arg Asp Ile Val 325 330 335 Ser Tyr Val Ile Asp His Phe Asp Ile Glu Ile Met Gly Gly Leu Gly 340 345 350 Pro Ser Thr Gly Lys Val Leu Arg Ile Gly Leu Leu Gly Cys Asn Ala 355 360 365 Thr Arg Glu Asn Val Asp Arg Val Thr Glu Ala Leu Arg Ala Ala Leu 370 375 380 Gln His Cys Pro Lys Lys Lys Leu 385 390 67 7280 DNA Homo Sapiens 67 agtcacccgg aggagttggt cgcacaatta tgaaagactc ggcttctgct gctagcgccg 60 gagctgagtt agtcctgaga aggtttccct gggcgttcct tgtccggcgg cctctgctgc 120 cgcctccgga gacgcttccc gatagatggc tacaggccgc ggaggaggag gaggtggagt 180 tgctgccctt ccggagtccg ccccgtgagg agaatgtccc agaaatcctg gatagaaagc 240 actttgacca agagggaatg tgtatatatt ataccaagtt ccaaggaccc tcacagatgc 300 cttccaggat gtcaaatttg tcagcaactc gtcaggtgtt tttgtggtcg cttggtcaag 360 caacatgctt gttttactgc aagtcttgcc atgaaatact cagatgtgaa attgggtgac 420 cattttaatc aggcaataga agaatggtct gtggaaaagc atacagaaca gagcccaacg 480 gatgcttatg gagtcataaa ttttcaaggg ggttctcatt cctacagagc taagtatgtg 540 aggctatcat atgacaccaa acctgaagtc attctgcaac ttctgcttaa agaatggcaa 600 atggagttac ccaaacttgt tatctctgta catgggggca tgcagaaatt tgagcttcac 660 ccacgaatca agcagttgct tggaaaaggt cttattaaag ctgcagttac aactggagcc 720 tggattttaa ctggaggagt aaacacaggt gtggcaaaac atgttggaga tgccctcaaa 780 gaacatgctt ccagatcatc tcgaaagatt tgcactatcg gaatagctcc atggggagtg 840 attgaaaaca gaaatgatct tgttgggaga gatgtggttg ctccttatca aaccttattg 900 aaccccctga gcaaattgaa tgttttgaat aatctgcatt cccatttcat attggtggat 960 gatggcactg ttggaaagta tggggcggaa gtcagactga gaagagaact tgaaaaaact 1020 attaatcagc aaagaattca tgctaggatt ggccagggtg tccctgtggt ggcacttata 1080 tttgagggtg ggccaaatgt tatcctcaca gttcttgaat accttcagga aagcccccct 1140 gttccagtag ttgtgtgtga aggaacaggc agagctgcag atctgctagc gtatattcat 1200 aaacaaacag aagaaggagg gaatcttcct gatgcagcag ggcacgatat tatttccact 1260 atcaaaaaaa catttaactt tggccagaat gaagcacttc atttatttca aacactgatg 1320 gagtgcatga aaagaaagga gcttatcact gttttccata ttgggtcaga tgaacatcaa 1380 gatatagatg tagcaatact tactgcactg ctaaaaggta ctaatgcatc tgcatttgac 1440 cagcttatcc ttacattggc atggggtaga gttgacattg ccaaaaatca tgtatttgtt 1500 tatggacagc agtggctggt tggatccttg gaacaagcta tgcttgatgc tcttgtaatg 1560 gatagagttg catttgtaaa acttcttatt gaaaatggag taagcatgca taaattcctt 1620 accattccga gactggaaga actttacaac actaaacaag gtccaactaa tccaatgctg 1680 tttcatcttg ttcgagacgt caaacaggga aatcttcctc caggatataa gatcactctg 1740 attgatatag gacttgttat tgaatatctc atgggaggaa cctacagatg cacctatact 1800 aggaaacgtt ttcgattaat atataatagt cttggtggaa ataatcggag gtctggccga 1860 aatacctcca gcagcactcc tcagttgcga aagagtcatg aatcttttgg caatagggca 1920 gataaaaagg aaaaaatgag gcataaccat ttcattaaga cagcacagcc ctaccgacca 1980 aagattgata cagttatgga agaaggaaag aagaaaagaa ccaaagatga aattgtagac 2040 attgatgatc cagaaaccaa gcgctttcct tatccactta atgaactttt aatttgggct 2100 tgccttatga agaggcaggt catggcccgt tttttatggc aacatggtga agaatcaatg 2160 gctaaagcat tagttgcctg taagatctat cgttcaatgg catatgaagc aaagcagagt 2220 gacctggtag atgatacttc agaagaacta aaacagtatt ccaatgattt tggtcagttg 2280 gccgttgaat tattagaaca gtccttcaga caagatgaaa ccatggctat gaaattgctc 2340 acttatgaac tgaagaactg gagtaattca acctgcctta agttagcagt ttcttcaaga 2400 cttagacctt ttgtagctca cacctgtaca caaatgttgt tatctgatat gtggatggga 2460 aggctgaata tgaggaaaaa ttcctggtac aaggtcatac taagcatttt agttccacct 2520 gccatattgc tgttagagta taaaactaag gctgaaatgt cccatatccc acaatctcaa 2580 gatgctcatc agatgtcaat ggatgacagc gaaaacaact ttcagaacat aacagaagag 2640 atccccatgg aagtgtttaa agaagtacgg attttggata gtaatgaagg aaagaatgag 2700 atggagatac aaatgaaatc aaaaaagctt ccaattacgc gaaagtttta tgccttttat 2760 catgcaccaa ttgtaaaatt ctggtttaac acgttggcat atttaggatt tctgatgctt 2820 tatacatttg tggttcttgt acaaatggaa cagttacctt cagttcaaga atggattgtt 2880 attgcttata tttttactta tgccattgag aaagtccgtg agatctttat gtctgaagct 2940 gggaaagtaa accagaagat taaagtatgg tttagtgatt acttcaacat cagtgataca 3000 attgccataa tttctttctt cattggattt ggactaagat ttggagcaaa atggaacttt 3060 gcaaatgcat atgataatca tgtttttgtg gctggaagat taatttactg tcttaacata 3120 atattttggt atgtgcgttt gctagatttt ctagctgtaa atcaacaggc aggaccttat 3180 gtaatgatga ttggaaaaat ggtggccaat atgttctaca ttgtagtgat tatggctctt 3240 gtattactta gttttggtgt tcccagaaag gcaatacttt atcctcatga agcaccatct 3300 tggactcttg ctaaagatat agtttttcac ccatactgga tgatttttgg tgaagtttat 3360 gcatacgaaa ttgatgtgtg tgcaaatgat tctgttatcc ctcaaatctg tggtcctggg 3420 acgtggttga ctccatttct tcaagcagtc tacctctttg tacagtatat cattatggtt 3480 aatcttctta ttgcattttt caacaatgtg tatttacaag tgaaggcaat ttccaatatt 3540 gtatggaagt accagcgtta tcattttatt atggcttatc atgagaaacc agttctgcct 3600 cctccactta tcattcttag ccatatagtt tctctgtttt gctgcatatg taagagaaga 3660 aagaaagata agacttccga tggaccaaaa cttttcttaa cagaagaaga tcaaaagaaa 3720 cttcatgatt ttgaagagca gtgtgttgaa atgtatttca atgaaaaaga tgacaaattt 3780 cattctggga gtgaagagag aattcgtgtc acttttgaaa gagtggaaca gatgtgcatt 3840 cagattaaag aagttggaga tcgtgtcaac tacataaaaa gatcattaca atcattagat 3900 tctcaaattg gccatttgca agatctttca gccctgacgg tagatacatt aaaaacactc 3960 actgcccaga aagcgtcgga agctagcaaa gttcataatg aaatcacacg agaactgagc 4020 atttccaaac acttggctca aaaccttatt gatgatggtc ctgtaagacc ttctgtatgg 4080 aaaaagcatg gtgttgtaaa tacacttagc tcctctcttc ctcaaggtga tcttgaaagt 4140 aataatcctt ttcattgtaa tattttaatg aaagatgaca aagatcccca gtgtaatata 4200 tttggtcaag acttacctgc agtaccccag agaaaagaat ttaattttcc agaggctggt 4260 tcctcttctg gtgccttatt cccaagtgct gtttcccctc cagaactgcg acagagacta 4320 catggggtag aactcttaaa aatatttaat aaaaatcaaa aattaggcag ttcatctact 4380 agcataccac atctgtcatc cccaccaacc aaattttttg ttagtacacc atctcagcca 4440 agttgcaaaa gccacttgga aactggaacc aaagatcaag aaactgtttg ctctaaagct 4500 acagaaggag ataatacaga atttggagca tttgtaggac acagagatag catggattta 4560 cagaggttta aagaaacatc aaacaagata aaaatactat ccgagcagca gaatgatgta 4620 agaaatgtga ttatggagta tacagagatg cctaaatatg agaataacaa tacttctgaa 4680 aacactttga aacgagtgag ttctcttgct ggatttactg actgtcacag aacttccatt 4740 cctgttcatt caaaacaagc agaaaaaatc agtagaaggc catctaccga agacactcat 4800 gaagtagatt ccaaagcagc tttaataccg gattggttac aagatagacc atcaaacaga 4860 gaaatgccat ctgaagaagg aacattaaat ggtctcactt ctccatttaa gccagctatg 4920 gatacaaatt actattattc agctgtggaa agaaataact tgatgaggtt atcacagagc 4980 attccattta cacctgtgcc tccaagaggg gagcctgtca cagtgtatcg tttggaagag 5040 agttcaccca acatactaaa taacagcatg tcttcttggt cacaactagg cctctgtgcc 5100 aaaatagagt ttttaagcaa agaggagatg ggaggaggtt tacgaagagc tgtcaaagta 5160 cagtgtacct ggtcagaaca tgatatcctc aaatcagggc atctttatat tatcaaatct 5220 tttcttccag aggtggttaa tacatggtca agtatttata aagaagatac agttctgcat 5280 ctctgtctga gagaaattca acaacagaga gcagcacaaa agcttacgtt tgcctttaat 5340 caaatgaaac ccaaatccat accatattct ccaaggttcc ttgaagtttt cctgctgtat 5400 tgccattcag caggacagtg gtttgctgtg gaagaatgta tgactggaga atttagaaaa 5460 tacaacaata ataatggaga tgagattatt ccaactaata ctctggaaga gatcatgcta 5520 gcctttagcc actggactta cgaatataca agaggggagt tactggtact tgatttgcaa 5580 ggtgttggtg aaaatttgac tgacccatct gtgataaaag cagaagaaaa gagatcctgt 5640 gatatggttt ttggcccagc aaatctagga gaagatgcaa ttaaaaactt cagagcaaaa 5700 catcactgta attcttgctg tagaaagctt aaacttccag atctgaagag gaatgattat 5760 acgcctgata aaattatatt tcctcaggat gagccttcag atttgaatct tcagcctgga 5820 aattccacca aagaatcaga atcaactaat tctgttcgtc tgatgttata atattaatat 5880 tactgaatca ttggttttgc ctgcacctca cagaaatgtt actgtgtcac ttttccctcg 5940 ggaggaaatt gtttggtaat atagaaaggt gtatgcaagt tgaatttgct gactccagca 6000 cagttaaaag gtcaatattc ttttgacctg attaatcagt cagaaagtcc ctataggata 6060 gagctggcag ctgagaaatt ttaaaggtaa ttgataatta gtatttgtaa ctttttaaag 6120 ggctctttgt atagcagagg atctcatttg actttgtttt gatgagggtg atgccctctc 6180 ttatgtggta caataccatt aaccaaaggt aggtgtccat gcagatttta ttggcagctg 6240 ttttattgcc attcaactag ggaaatgaag aaatcacgca gccttttggt taaatggcag 6300 tcaaaatttt cctcagtgta tttagtgtgt tcagtgatga tatcactggt tcccaactag 6360 atgcttgttg gccacgggaa gggaaatgac ttgttctaat tctaggttca cagaggtatg 6420 agaagcctga actgaagacc attttcaaga gggacggtat ttatgaatca gggttaggct 6480 ccatatttaa agatagagcc agtttttttt tttaaataga acccaaattg tgtaaaaatg 6540 ttaattgggt tttttaaaca ttgttttatc aagtcactgt taagtagaag aaagccatgg 6600 taaactgata cataacctaa attataaaag cagaaaccta actcactcgt caagggaagt 6660 taccttttga ggaaagttaa agtacttttt tccctatctg tatctatagc aacaacccag 6720 aacttacaaa cttctccaaa gattttattg attgttatat caaatcagaa tgtaaacatg 6780 aactcttgca tatatttaaa attgtgttgg aacatttgaa catgaatgct gtttgtggta 6840 cttaagaaat taattcagtt ggattatcat tatgtgatac tggcagattg cagtgcaacc 6900 ttatgccaat aaaatgtaat ttaacagccc cagatattgt tgaatattca acaataacaa 6960 gaaaagcttt tcatctaagt tttatgcttt aatttttttt cttttttttt ctttttcttt 7020 tgtttccttg gtactaattt taatttttat ttggaaggga gcagtataaa gcttatttgt 7080 atttagtagt gtatctcata gatacagaca aggcaagaga tgataagctg tttaaatagt 7140 gtttaatatt gattgggggt ggggagaaag aaaaagtgta ttacttaaag atactatata 7200 cgttttgtat atcattaaat ctttaaaaga aatgaaataa atttattgtt tacagatgaa 7260 aaaaaaaaaa aaaaaaaaaa 7280 68 1885 PRT Homo Sapiens 68 Met Ser Gln Lys Ser Trp Ile Glu Ser Thr Leu Thr Lys Arg Glu Cys 1 5 10 15 Val Tyr Ile Ile Pro Ser Ser Lys Asp Pro His Arg Cys Leu Pro Gly 20 25 30 Cys Gln Ile Cys Gln Gln Leu Val Arg Cys Phe Cys Gly Arg Leu Val 35 40 45 Lys Gln His Ala Cys Phe Thr Ala Ser Leu Ala Met Lys Tyr Ser Asp 50 55 60 Val Lys Leu Gly Asp His Phe Asn Gln Ala Ile Glu Glu Trp Ser Val 65 70 75 80 Glu Lys His Thr Glu Gln Ser Pro Thr Asp Ala Tyr Gly Val Ile Asn 85 90 95 Phe Gln Gly Gly Ser His Ser Tyr Arg Ala Lys Tyr Val Arg Leu Ser 100 105 110 Tyr Asp Thr Lys Pro Glu Val Ile Leu Gln Leu Leu Leu Lys Glu Trp 115 120 125 Gln Met Glu Leu Pro Lys Leu Val Ile Ser Val His Gly Gly Met Gln 130 135 140 Lys Phe Glu Leu His Pro Arg Ile Lys Gln Leu Leu Gly Lys Gly Leu 145 150 155 160 Ile Lys Ala Ala Val Thr Thr Gly Ala Trp Ile Leu Thr Gly Gly Val 165 170 175 Asn Thr Gly Val Ala Lys His Val Gly Asp Ala Leu Lys Glu His Ala 180 185 190 Ser Arg Ser Ser Arg Lys Ile Cys Thr Ile Gly Ile Ala Pro Trp Gly 195 200 205 Val Ile Glu Asn Arg Asn Asp Leu Val Gly Arg Asp Val Val Ala Pro 210 215 220 Tyr Gln Thr Leu Leu Asn Pro Leu Ser Lys Leu Asn Val Leu Asn Asn 225 230 235 240 Leu His Ser His Phe Ile Leu Val Asp Asp Gly Thr Val Gly Lys Tyr 245 250 255 Gly Ala Glu Val Arg Leu Arg Arg Glu Leu Glu Lys Thr Ile Asn Gln 260 265 270 Gln Arg Ile His Ala Arg Ile Gly Gln Gly Val Pro Val Val Ala Leu 275 280 285 Ile Phe Glu Gly Gly Pro Asn Val Ile Leu Thr Val Leu Glu Tyr Leu 290 295 300 Gln Glu Ser Pro Pro Val Pro Val Val Val Cys Glu Gly Thr Gly Arg 305 310 315 320 Ala Ala Asp Leu Leu Ala Tyr Ile His Lys Gln Thr Glu Glu Gly Gly 325 330 335 Asn Leu Pro Asp Ala Ala Gly His Asp Ile Ile Ser Thr Ile Lys Lys 340 345 350 Thr Phe Asn Phe Gly Gln Asn Glu Ala Leu His Leu Phe Gln Thr Leu 355 360 365 Met Glu Cys Met Lys Arg Lys Glu Leu Ile Thr Val Phe His Ile Gly 370 375 380 Ser Asp Glu His Gln Asp Ile Asp Val Ala Ile Leu Thr Ala Leu Leu 385 390 395 400 Lys Gly Thr Asn Ala Ser Ala Phe Asp Gln Leu Ile Leu Thr Leu Ala 405 410 415 Trp Gly Arg Val Asp Ile Ala Lys Asn His Val Phe Val Tyr Gly Gln 420 425 430 Gln Trp Leu Val Gly Ser Leu Glu Gln Ala Met Leu Asp Ala Leu Val 435 440 445 Met Asp Arg Val Ala Phe Val Lys Leu Leu Ile Glu Asn Gly Val Ser 450 455 460 Met His Lys Phe Leu Thr Ile Pro Arg Leu Glu Glu Leu Tyr Asn Thr 465 470 475 480 Lys Gln Gly Pro Thr Asn Pro Met Leu Phe His Leu Val Arg Asp Val 485 490 495 Lys Gln Gly Asn Leu Pro Pro Gly Tyr Lys Ile Thr Leu Ile Asp Ile 500 505 510 Gly Leu Val Ile Glu Tyr Leu Met Gly Gly Thr Tyr Arg Cys Thr Tyr 515 520 525 Thr Arg Lys Arg Phe Arg Leu Ile Tyr Asn Ser Leu Gly Gly Asn Asn 530 535 540 Arg Arg Ser Gly Arg Asn Thr Ser Ser Ser Thr Pro Gln Leu Arg Lys 545 550 555 560 Ser His Glu Ser Phe Gly Asn Arg Ala Asp Lys Lys Glu Lys Met Arg 565 570 575 His Asn His Phe Ile Lys Thr Ala Gln Pro Tyr Arg Pro Lys Ile Asp 580 585 590 Thr Val Met Glu Glu Gly Lys Lys Lys Arg Thr Lys Asp Glu Ile Val 595 600 605 Asp Ile Asp Asp Pro Glu Thr Lys Arg Phe Pro Tyr Pro Leu Asn Glu 610 615 620 Leu Leu Ile Trp Ala Cys Leu Met Lys Arg Gln Val Met Ala Arg Phe 625 630 635 640 Leu Trp Gln His Gly Glu Glu Ser Met Ala Lys Ala Leu Val Ala Cys 645 650 655 Lys Ile Tyr Arg Ser Met Ala Tyr Glu Ala Lys Gln Ser Asp Leu Val 660 665 670 Asp Asp Thr Ser Glu Glu Leu Lys Gln Tyr Ser Asn Asp Phe Gly Gln 675 680 685 Leu Ala Val Glu Leu Leu Glu Gln Ser Phe Arg Gln Asp Glu Thr Met 690 695 700 Ala Met Lys Leu Leu Thr Tyr Glu Leu Lys Asn Trp Ser Asn Ser Thr 705 710 715 720 Cys Leu Lys Leu Ala Val Ser Ser Arg Leu Arg Pro Phe Val Ala His 725 730 735 Thr Cys Thr Gln Met Leu Leu Ser Asp Met Trp Met Gly Arg Leu Asn 740 745 750 Met Arg Lys Asn Ser Trp Tyr Lys Val Ile Leu Ser Ile Leu Val Pro 755 760 765 Pro Ala Ile Leu Leu Leu Glu Tyr Lys Thr Lys Ala Glu Met Ser His 770 775 780 Ile Pro Gln Ser Gln Asp Ala His Gln Met Ser Met Asp Asp Ser Glu 785 790 795 800 Asn Asn Phe Gln Asn Ile Thr Glu Glu Ile Pro Met Glu Val Phe Lys 805 810 815 Glu Val Arg Ile Leu Asp Ser Asn Glu Gly Lys Asn Glu Met Glu Ile 820 825 830 Gln Met Lys Ser Lys Lys Leu Pro Ile Thr Arg Lys Phe Tyr Ala Phe 835 840 845 Tyr His Ala Pro Ile Val Lys Phe Trp Phe Asn Thr Leu Ala Tyr Leu 850 855 860 Gly Phe Leu Met Leu Tyr Thr Phe Val Val Leu Val Gln Met Glu Gln 865 870 875 880 Leu Pro Ser Val Gln Glu Trp Ile Val Ile Ala Tyr Ile Phe Thr Tyr 885 890 895 Ala Ile Glu Lys Val Arg Glu Ile Phe Met Ser Glu Ala Gly Lys Val 900 905 910 Asn Gln Lys Ile Lys Val Trp Phe Ser Asp Tyr Phe Asn Ile Ser Asp 915 920 925 Thr Ile Ala Ile Ile Ser Phe Phe Ile Gly Phe Gly Leu Arg Phe Gly 930 935 940 Ala Lys Trp Asn Phe Ala Asn Ala Tyr Asp Asn His Val Phe Val Ala 945 950 955 960 Gly Arg Leu Ile Tyr Cys Leu Asn Ile Ile Phe Trp Tyr Val Arg Leu 965 970 975 Leu Asp Phe Leu Ala Val Asn Gln Gln Ala Gly Pro Tyr Val Met Met 980 985 990 Ile Gly Lys Met Val Ala Asn Met Phe Tyr Ile Val Val Ile Met Ala 995 1000 1005 Leu Val Leu Leu Ser Phe Gly Val Pro Arg Lys Ala Ile Leu Tyr Pro 1010 1015 1020 His Glu Ala Pro Ser Trp Thr Leu Ala Lys Asp Ile Val Phe His Pro 1025 1030 1035 1040 Tyr Trp Met Ile Phe Gly Glu Val Tyr Ala Tyr Glu Ile Asp Val Cys 1045 1050 1055 Ala Asn Asp Ser Val Ile Pro Gln Ile Cys Gly Pro Gly Thr Trp Leu 1060 1065 1070 Thr Pro Phe Leu Gln Ala Val Tyr Leu Phe Val Gln Tyr Ile Ile Met 1075 1080 1085 Val Asn Leu Leu Ile Ala Phe Phe Asn Asn Val Tyr Leu Gln Val Lys 1090 1095 1100 Ala Ile Ser Asn Ile Val Trp Lys Tyr Gln Arg Tyr His Phe Ile Met 1105 1110 1115 1120 Ala Tyr His Glu Lys Pro Val Leu Pro Pro Pro Leu Ile Ile Leu Ser 1125 1130 1135 His Ile Val Ser Leu Phe Cys Cys Ile Cys Lys Arg Arg Lys Lys Asp 1140 1145 1150 Lys Thr Ser Asp Gly Pro Lys Leu Phe Leu Thr Glu Glu Asp Gln Lys 1155 1160 1165 Lys Leu His Asp Phe Glu Glu Gln Cys Val Glu Met Tyr Phe Asn Glu 1170 1175 1180 Lys Asp Asp Lys Phe His Ser Gly Ser Glu Glu Arg Ile Arg Val Thr 1185 1190 1195 1200 Phe Glu Arg Val Glu Gln Met Cys Ile Gln Ile Lys Glu Val Gly Asp 1205 1210 1215 Arg Val Asn Tyr Ile Lys Arg Ser Leu Gln Ser Leu Asp Ser Gln Ile 1220 1225 1230 Gly His Leu Gln Asp Leu Ser Ala Leu Thr Val Asp Thr Leu Lys Thr 1235 1240 1245 Leu Thr Ala Gln Lys Ala Ser Glu Ala Ser Lys Val His Asn Glu Ile 1250 1255 1260 Thr Arg Glu Leu Ser Ile Ser Lys His Leu Ala Gln Asn Leu Ile Asp 1265 1270 1275 1280 Asp Gly Pro Val Arg Pro Ser Val Trp Lys Lys His Gly Val Val Asn 1285 1290 1295 Thr Leu Ser Ser Ser Leu Pro Gln Gly Asp Leu Glu Ser Asn Asn Pro 1300 1305 1310 Phe His Cys Asn Ile Leu Met Lys Asp Asp Lys Asp Pro Gln Cys Asn 1315 1320 1325 Ile Phe Gly Gln Asp Leu Pro Ala Val Pro Gln Arg Lys Glu Phe Asn 1330 1335 1340 Phe Pro Glu Ala Gly Ser Ser Ser Gly Ala Leu Phe Pro Ser Ala Val 1345 1350 1355 1360 Ser Pro Pro Glu Leu Arg Gln Arg Leu His Gly Val Glu Leu Leu Lys 1365 1370 1375 Ile Phe Asn Lys Asn Gln Lys Leu Gly Ser Ser Ser Thr Ser Ile Pro 1380 1385 1390 His Leu Ser Ser Pro Pro Thr Lys Phe Phe Val Ser Thr Pro Ser Gln 1395 1400 1405 Pro Ser Cys Lys Ser His Leu Glu Thr Gly Thr Lys Asp Gln Glu Thr 1410 1415 1420 Val Cys Ser Lys Ala Thr Glu Gly Asp Asn Thr Glu Phe Gly Ala Phe 1425 1430 1435 1440 Val Gly His Arg Asp Ser Met Asp Leu Gln Arg Phe Lys Glu Thr Ser 1445 1450 1455 Asn Lys Ile Lys Ile Leu Ser Glu Gln Gln Asn Asp Val Arg Asn Val 1460 1465 1470 Ile Met Glu Tyr Thr Glu Met Pro Lys Tyr Glu Asn Asn Asn Thr Ser 1475 1480 1485 Glu Asn Thr Leu Lys Arg Val Ser Ser Leu Ala Gly Phe Thr Asp Cys 1490 1495 1500 His Arg Thr Ser Ile Pro Val His Ser Lys Gln Ala Glu Lys Ile Ser 1505 1510 1515 1520 Arg Arg Pro Ser Thr Glu Asp Thr His Glu Val Asp Ser Lys Ala Ala 1525 1530 1535 Leu Ile Pro Asp Trp Leu Gln Asp Arg Pro Ser Asn Arg Glu Met Pro 1540 1545 1550 Ser Glu Glu Gly Thr Leu Asn Gly Leu Thr Ser Pro Phe Lys Pro Ala 1555 1560 1565 Met Asp Thr Asn Tyr Tyr Tyr Ser Ala Val Glu Arg Asn Asn Leu Met 1570 1575 1580 Arg Leu Ser Gln Ser Ile Pro Phe Thr Pro Val Pro Pro Arg Gly Glu 1585 1590 1595 1600 Pro Val Thr Val Tyr Arg Leu Glu Glu Ser Ser Pro Asn Ile Leu Asn 1605 1610 1615 Asn Ser Met Ser Ser Trp Ser Gln Leu Gly Leu Cys Ala Lys Ile Glu 1620 1625 1630 Phe Leu Ser Lys Glu Glu Met Gly Gly Gly Leu Arg Arg Ala Val Lys 1635 1640 1645 Val Gln Cys Thr Trp Ser Glu His Asp Ile Leu Lys Ser Gly His Leu 1650 1655 1660 Tyr Ile Ile Lys Ser Phe Leu Pro Glu Val Val Asn Thr Trp Ser Ser 1665 1670 1675 1680 Ile Tyr Lys Glu Asp Thr Val Leu His Leu Cys Leu Arg Glu Ile Gln 1685 1690 1695 Gln Gln Arg Ala Ala Gln Lys Leu Thr Phe Ala Phe Asn Gln Met Lys 1700 1705 1710 Pro Lys Ser Ile Pro Tyr Ser Pro Arg Phe Leu Glu Val Phe Leu Leu 1715 1720 1725 Tyr Cys His Ser Ala Gly Gln Trp Phe Ala Val Glu Glu Cys Met Thr 1730 1735 1740 Gly Glu Phe Arg Lys Tyr Asn Asn Asn Asn Gly Asp Glu Ile Ile Pro 1745 1750 1755 1760 Thr Asn Thr Leu Glu Glu Ile Met Leu Ala Phe Ser His Trp Thr Tyr 1765 1770 1775 Glu Tyr Thr Arg Gly Glu Leu Leu Val Leu Asp Leu Gln Gly Val Gly 1780 1785 1790 Glu Asn Leu Thr Asp Pro Ser Val Ile Lys Ala Glu Glu Lys Arg Ser 1795 1800 1805 Cys Asp Met Val Phe Gly Pro Ala Asn Leu Gly Glu Asp Ala Ile Lys 1810 1815 1820 Asn Phe Arg Ala Lys His His Cys Asn Ser Cys Cys Arg Lys Leu Lys 1825 1830 1835 1840 Leu Pro Asp Leu Lys Arg Asn Asp Tyr Thr Pro Asp Lys Ile Ile Phe 1845 1850 1855 Pro Gln Asp Glu Pro Ser Asp Leu Asn Leu Gln Pro Gly Asn Ser Thr 1860 1865 1870 Lys Glu Ser Glu Ser Thr Asn Ser Val Arg Leu Met Leu 1875 1880 1885 69 1696 DNA Homo Sapiens 69 gcacgagggt gatgaaggcc tacgagtgcg gcgcggcctg aaggggcacg cgggggacct 60 gcaaagctag tgaggggcgg ggcaggcggc gcggtggggg cgggccgagc ccggaggcca 120 gatgagcgga cacagcccca cgcgcggggc catgcaggtg gccatgaacg gtaaggcccg 180 caaagaggcg gtgcagactg cggctaagga actcctcaag ttcgtgaacc ggagtccctc 240 tcctttccat gctgtggctg aatgccgcaa ccgccttctc caggctggct tcagtgaact 300 caaggagact gagaaatgga atattaagcc cgagagcaag tacttcatga ccaggaactc 360 ctccaccatc atagcttttg ctgtaggggg ccagtacgtt cctggcaatg gcttcagcct 420 catcggggcc cacacggaca gcccctgcct ccgggtgaaa cgtcggtctc gccgcagcca 480 ggtgggcttc cagcaagtcg gtgtggagac ctatggtggt gggatctgga gcacctggtt 540 tgaccgtgac ctgactctgg ctggacgcgt cattgtcaag tgccctacct caggtcggct 600 ggagcagcag ctggtgcacg tggagcggcc cattcttcgc atcccacacc tggccatcca 660 tctgcagcga aatatcaacg agaactttgg gcccaacaca gagatgcatc tagtccccat 720 tcttgccaca gccatccagg aggagctgga gaaggggact cctgagccag ggcctctcaa 780 tgctgtggat gagcggcacc attcggtcct catgtccctg ctctgtgccc atctggggct 840 gagccccaag gacatagtgg agatggagct ctgccttgca gacacccagc ctgcggtctt 900 gggtggtgcc tatgatgagt tcatctttgc tcctcggctg gacaatctgc acagctgctt 960 ctgtgccctg caggccttga tagattcctg tgcaggccct ggctccctgg ccacagagcc 1020 tcacgtgcgc atggtcacac tctatgacaa cgaagaggtg gggtctgaga gtgcacaggg 1080 agcacagtca ctgctgacag agctggtgct gcggcggatc tcagcctcgt gccagcaccc 1140 gacagccttc gaggaagcca tacccaagtc cttcatgatc agcgcagaca tggcccatgc 1200 tgtgcatccc aactacctgg acaagcatga ggagaaccac cggcctttat tccacaaggg 1260 ccccgtgatc aaggtgaaca gcaagcaacg ctatgcttca aacgcggtgt cagaggccct 1320 gatccgagag gtggccaaca aagtcaaggt ccccctgcag gatctcatgg tccggaatga 1380 caccccctgt ggaaccacca ttggacctat cttggcttct cggctggggc tgcgggtgct 1440 ggatttaggc agcccccaac tggccatgca ctctatccgg gagatggcct gcaccacagg 1500 agtcctccag accctcaccc tcttcaaggg cttctttgag ctgttccctt ctctaagcca 1560 taatctctta gtggattgag ccctcttgga aagacttctc tgccatccct ttgcacctga 1620 gaggggaagt tctcagctga gctgaagctg gattattaaa gtggattgtc actcagaaaa 1680 aaaaaaaaaa aaaaaa 1696 70 475 PRT Homo Sapiens 70 Met Gln Val Ala Met Asn Gly Lys Ala Arg Lys Glu Ala Val Gln Thr 1 5 10 15 Ala Ala Lys Glu Leu Leu Lys Phe Val Asn Arg Ser Pro Ser Pro Phe 20 25 30 His Ala Val Ala Glu Cys Arg Asn Arg Leu Leu Gln Ala Gly Phe Ser 35 40 45 Glu Leu Lys Glu Thr Glu Lys Trp Asn Ile Lys Pro Glu Ser Lys Tyr 50 55 60 Phe Met Thr Arg Asn Ser Ser Thr Ile Ile Ala Phe Ala Val Gly Gly 65 70 75 80 Gln Tyr Val Pro Gly Asn Gly Phe Ser Leu Ile Gly Ala His Thr Asp 85 90 95 Ser Pro Cys Leu Arg Val Lys Arg Arg Ser Arg Arg Ser Gln Val Gly 100 105 110 Phe Gln Gln Val Gly Val Glu Thr Tyr Gly Gly Gly Ile Trp Ser Thr 115 120 125 Trp Phe Asp Arg Asp Leu Thr Leu Ala Gly Arg Val Ile Val Lys Cys 130 135 140 Pro Thr Ser Gly Arg Leu Glu Gln Gln Leu Val His Val Glu Arg Pro 145 150 155 160 Ile Leu Arg Ile Pro His Leu Ala Ile His Leu Gln Arg Asn Ile Asn 165 170 175 Glu Asn Phe Gly Pro Asn Thr Glu Met His Leu Val Pro Ile Leu Ala 180 185 190 Thr Ala Ile Gln Glu Glu Leu Glu Lys Gly Thr Pro Glu Pro Gly Pro 195 200 205 Leu Asn Ala Val Asp Glu Arg His His Ser Val Leu Met Ser Leu Leu 210 215 220 Cys Ala His Leu Gly Leu Ser Pro Lys Asp Ile Val Glu Met Glu Leu 225 230 235 240 Cys Leu Ala Asp Thr Gln Pro Ala Val Leu Gly Gly Ala Tyr Asp Glu 245 250 255 Phe Ile Phe Ala Pro Arg Leu Asp Asn Leu His Ser Cys Phe Cys Ala 260 265 270 Leu Gln Ala Leu Ile Asp Ser Cys Ala Gly Pro Gly Ser Leu Ala Thr 275 280 285 Glu Pro His Val Arg Met Val Thr Leu Tyr Asp Asn Glu Glu Val Gly 290 295 300 Ser Glu Ser Ala Gln Gly Ala Gln Ser Leu Leu Thr Glu Leu Val Leu 305 310 315 320 Arg Arg Ile Ser Ala Ser Cys Gln His Pro Thr Ala Phe Glu Glu Ala 325 330 335 Ile Pro Lys Ser Phe Met Ile Ser Ala Asp Met Ala His Ala Val His 340 345 350 Pro Asn Tyr Leu Asp Lys His Glu Glu Asn His Arg Pro Leu Phe His 355 360 365 Lys Gly Pro Val Ile Lys Val Asn Ser Lys Gln Arg Tyr Ala Ser Asn 370 375 380 Ala Val Ser Glu Ala Leu Ile Arg Glu Val Ala Asn Lys Val Lys Val 385 390 395 400 Pro Leu Gln Asp Leu Met Val Arg Asn Asp Thr Pro Cys Gly Thr Thr 405 410 415 Ile Gly Pro Ile Leu Ala Ser Arg Leu Gly Leu Arg Val Leu Asp Leu 420 425 430 Gly Ser Pro Gln Leu Ala Met His Ser Ile Arg Glu Met Ala Cys Thr 435 440 445 Thr Gly Val Leu Gln Thr Leu Thr Leu Phe Lys Gly Phe Phe Glu Leu 450 455 460 Phe Pro Ser Leu Ser His Asn Leu Leu Val Asp 465 470 475 71 2327 DNA Homo Sapiens 71 aatgccaagt gatggcaact gcctcccgcc gcgtctccag ccggtgcggg gaacgagacc 60 ctgcggagat taccagtacg tggggaagtt ggcgggcagg aattcagaat ccattgaggc 120 cttcactcac cactttccct ctctcgctgt gttcccaaat gtgccacttt tctgttggct 180 cacatgcacc catgctctat ttgatattca gggctctgaa tttcaagcca gactcagtca 240 gtgtgattgt cactgctttc ctgtccttcc tttatcatct gtagacttgg gtcccgtttt 300 tgcaggttga tgttctgtct tcgctgggct ctggactcac tgctcacgag tgcggtgtct 360 gcatgggcac tgcccagaca tgcactgttg gtccctcgat ggctgcatgg tcaggcctca 420 gggctctctg ccaggccgac ctacagccca tacagacctg atttctgggc ctggatccag 480 gggatgccat ctgggaagtg cgggatcttc ccacgatgtc actgtaaaac tcaccaggga 540 ggttttagaa attgaaccgg catcattcag attccatcct gctttttggt cctgagaaaa 600 tcctgctttt ccctgagtaa ctgggataat gggtcaccag ctcccatgcc ctagatgagg 660 actagttagc attttctagt gcctggagat ttccagatgg aagctgtact tgggtctgtg 720 tatctttgtt acaggattca ataattcatg cactgaattt cccttcccgg caactccaga 780 caccaaatcg cttcccatgg tgtcccccaa tcacttagga atttagcctg tgtctaaaga 840 ccctctctgc agcctgacgt ggctagccat cccagtactt ccacgttttt catgcctttc 900 tccaacagcg ttgccgtggc cccttaggcg gcgatcgttt tatcaatggt cgctccctct 960 ttttatctgt tggcaggagc cctttttcaa cgccctcgct ggagtctggc ctgcacgcct 1020 tgctgaatga agccggaacc tcagccccgc ttccctttga aatgaatgtt cctggggcgc 1080 cctctcgtgg attttggagc taatcgtctg tgaatgccaa gtgatggcaa ctgccctccc 1140 gccgcgtctc cagccggtgc gggggaacga gaccctgcgg gagcattacc agtacgtggg 1200 gaagttggcg ggcaggctga aggaggcctc cgagggcagc acgctcacca ccgtgctctt 1260 cttggtcatc tgcagcttca tcgtcttgga gaacctgatg gttttgattg ccatctggaa 1320 aaacaataaa tttcacaacc gcatgtactt tttcattggc aacctggctc tctgcgacct 1380 gctggccggc atcgcttaca aggtcaacat tctgatgtct ggcaagaaga cgttcagcct 1440 gtctcccacg gtctggttcc tcagggaggg cagtatgttc gtggcccttg gggcgtccac 1500 ctgcagctta ctggccatcg ccatcgagcg gcacttgaca atgatcaaaa tgaggcctta 1560 cgacgccaac aagaggcacc gcgtcttcct cctgatcggg atgtgctggc tcattgcctt 1620 cacgctgggc gccctgccca ttctgggctg gaactgcctg cacaatctcc ctgactgctc 1680 taccatcctg cccctctact ccaagaagta cattgccttc tgcatcagca tcttcacggc 1740 catcctggtg accatcgtga tcctctacgc acgcatctac ttcctggtga agtccagcag 1800 ccgtaaggtg gccaaccaca acaactcgga gcggtccatg gcactgctgc ggaccgtggt 1860 gattgtggtg agcgtgttca tcgcctgctg gtccccactc ttcatcctct tcctcattga 1920 tgtggcctgc agggtgcagg cgtgccccat cctcttcaag gctcagtggt tcatcgtgtt 1980 ggctgtgctc aactccgcca tgaacccggt catctacacg ctggccagca aggagatgcg 2040 gcgggccttc ttccgtctgg tctgcaactg cctggtcagg ggacgggggg cccgcgcctc 2100 acccatccag cctgcgctcg acccaagcag aagtaaatca agcagcagca acaatagcag 2160 ccactctccg aaggtcaagg aagacctgcc ccacacagac ccctcatcct gcatcatgga 2220 caagaacgca gcacttcaga atgggatctt ctgcaactga tcgtctccat gcgccctgct 2280 ctgcggctgt gttcttattt attgcatgcg tcgcttccac aggggcc 2327 72 378 PRT Homo Sapiens 72 Met Ala Thr Ala Leu Pro Pro Arg Leu Gln Pro Val Arg Gly Asn Glu 1 5 10 15 Thr Leu Arg Glu His Tyr Gln Tyr Val Gly Lys Leu Ala Gly Arg Leu 20 25 30 Lys Glu Ala Ser Glu Gly Ser Thr Leu Thr Thr Val Leu Phe Leu Val 35 40 45 Ile Cys Ser Phe Ile Val Leu Glu Asn Leu Met Val Leu Ile Ala Ile 50 55 60 Trp Lys Asn Asn Lys Phe His Asn Arg Met Tyr Phe Phe Ile Gly Asn 65 70 75 80 Leu Ala Leu Cys Asp Leu Leu Ala Gly Ile Ala Tyr Lys Val Asn Ile 85 90 95 Leu Met Ser Gly Lys Lys Thr Phe Ser Leu Ser Pro Thr Val Trp Phe 100 105 110 Leu Arg Glu Gly Ser Met Phe Val Ala Leu Gly Ala Ser Thr Cys Ser 115 120 125 Leu Leu Ala Ile Ala Ile Glu Arg His Leu Thr Met Ile Lys Met Arg 130 135 140 Pro Tyr Asp Ala Asn Lys Arg His Arg Val Phe Leu Leu Ile Gly Met 145 150 155 160 Cys Trp Leu Ile Ala Phe Thr Leu Gly Ala Leu Pro Ile Leu Gly Trp 165 170 175 Asn Cys Leu His Asn Leu Pro Asp Cys Ser Thr Ile Leu Pro Leu Tyr 180 185 190 Ser Lys Lys Tyr Ile Ala Phe Cys Ile Ser Ile Phe Thr Ala Ile Leu 195 200 205 Val Thr Ile Val Ile Leu Tyr Ala Arg Ile Tyr Phe Leu Val Lys Ser 210 215 220 Ser Ser Arg Lys Val Ala Asn His Asn Asn Ser Glu Arg Ser Met Ala 225 230 235 240 Leu Leu Arg Thr Val Val Ile Val Val Ser Val Phe Ile Ala Cys Trp 245 250 255 Ser Pro Leu Phe Ile Leu Phe Leu Ile Asp Val Ala Cys Arg Val Gln 260 265 270 Ala Cys Pro Ile Leu Phe Lys Ala Gln Trp Phe Ile Val Leu Ala Val 275 280 285 Leu Asn Ser Ala Met Asn Pro Val Ile Tyr Thr Leu Ala Ser Lys Glu 290 295 300 Met Arg Arg Ala Phe Phe Arg Leu Val Cys Asn Cys Leu Val Arg Gly 305 310 315 320 Arg Gly Ala Arg Ala Ser Pro Ile Gln Pro Ala Leu Asp Pro Ser Arg 325 330 335 Ser Lys Ser Ser Ser Ser Asn Asn Ser Ser His Ser Pro Lys Val Lys 340 345 350 Glu Asp Leu Pro His Thr Asp Pro Ser Ser Cys Ile Met Asp Lys Asn 355 360 365 Ala Ala Leu Gln Asn Gly Ile Phe Cys Asn 370 375 73 1576 DNA Homo Sapiens 73 tcaccaccta caaccacaga gctgtcatgg ctgccatctc tacttccatc cctgtaattt 60 cacagcccca gttcacagcc atgaatgaac cacagtgctt ctacaacgag tccattgcct 120 tcttttataa ccgaagtgga aagcatcttg ccacagaatg gaacacagtc agcaagctgg 180 tgatgggact tggaatcact gtttgtatct tcatcatgtt ggccaaccta ttggtcatgg 240 tggcaatcta tgtcaaccgc cgcttccatt ttcctattta ttacctaatg gctaatctgg 300 ctgctgcaga cttctttgct gggttggcct acttctatct catgttcaac acaggaccca 360 atactcggag actgactgtt agcacatggc tcctgcgtca gggcctcatt gacaccagcc 420 tgacggcatc tgtggccaac ttactggcta ttgcaatcga gaggcacatt acggttttcc 480 gcatgcagct ccacacacgg atgagcaacc ggcgggtagt ggtggtcatt gtggtcatct 540 ggactatggc catcgttatg ggtgctatac ccagtgtggg ctggaactgt atctgtgata 600 ttgaaaattg ttccaacatg gcacccctct acagtgactc ttacttagtc ttctgggcca 660 ttttcaactt ggtgaccttt gtggtaatgg tggttctcta tgctcacatc tttggctatg 720 ttcgccagag gactatgaga atgtctcggc atagttctgg accccggcgg aatcgggata 780 ccatgatgag tcttctgaag actgtggtca ttgtgcttgg ggcctttatc atctgctgga 840 ctcctggatt ggttttgtta cttctagacg tgtgctgtcc acagtgcgac gtgctggcct 900 atgagaaatt cttccttctc cttgctgaat tcaactctgc catgaacccc atcatttact 960 cctaccgcga caaagaaatg agcgccacct ttaggcagat cctctgctgc cagcgcagtg 1020 agaaccccac cggccccaca gaaagctcag accgctcggc ttcctccctc aaccacacca 1080 tcttggctgg agttcacagc aatgaccact ctgtggttta gaacggaaac tgagatgagg 1140 aaccagccgt cctctcttgg aggataaaca gcctccccct acccaattgc cagggcaagg 1200 tggggtgtga gagaggagaa aagtcaactc atgtacttaa acactaacca atgacagtat 1260 ttgttcctgg accccacaag acttgatata tattgaaaat tagcttatgt gacaaccctc 1320 atcttgatcc ccatcccttc tgaaagtagg aagttggagc tcttgcaatg gaattcaaga 1380 acagactctg gagtgtccat ttagactaca ctaactagac ttttaaaaga ttttgtgtgg 1440 tttggtgcaa gtcagaataa attctggcta gttgaatcca caacttcatt tatatacagg 1500 cttccctttt ttatttttaa aggatacgtt tcacttaata aacacgttta tgcctatcag 1560 caaaaaaaaa aaaaaa 1576 74 364 PRT Homo Sapiens 74 Met Ala Ala Ile Ser Thr Ser Ile Pro Val Ile Ser Gln Pro Gln Phe 1 5 10 15 Thr Ala Met Asn Glu Pro Gln Cys Phe Tyr Asn Glu Ser Ile Ala Phe 20 25 30 Phe Tyr Asn Arg Ser Gly Lys His Leu Ala Thr Glu Trp Asn Thr Val 35 40 45 Ser Lys Leu Val Met Gly Leu Gly Ile Thr Val Cys Ile Phe Ile Met 50 55 60 Leu Ala Asn Leu Leu Val Met Val Ala Ile Tyr Val Asn Arg Arg Phe 65 70 75 80 His Phe Pro Ile Tyr Tyr Leu Met Ala Asn Leu Ala Ala Ala Asp Phe 85 90 95 Phe Ala Gly Leu Ala Tyr Phe Tyr Leu Met Phe Asn Thr Gly Pro Asn 100 105 110 Thr Arg Arg Leu Thr Val Ser Thr Trp Leu Leu Arg Gln Gly Leu Ile 115 120 125 Asp Thr Ser Leu Thr Ala Ser Val Ala Asn Leu Leu Ala Ile Ala Ile 130 135 140 Glu Arg His Ile Thr Val Phe Arg Met Gln Leu His Thr Arg Met Ser 145 150 155 160 Asn Arg Arg Val Val Val Val Ile Val Val Ile Trp Thr Met Ala Ile 165 170 175 Val Met Gly Ala Ile Pro Ser Val Gly Trp Asn Cys Ile Cys Asp Ile 180 185 190 Glu Asn Cys Ser Asn Met Ala Pro Leu Tyr Ser Asp Ser Tyr Leu Val 195 200 205 Phe Trp Ala Ile Phe Asn Leu Val Thr Phe Val Val Met Val Val Leu 210 215 220 Tyr Ala His Ile Phe Gly Tyr Val Arg Gln Arg Thr Met Arg Met Ser 225 230 235 240 Arg His Ser Ser Gly Pro Arg Arg Asn Arg Asp Thr Met Met Ser Leu 245 250 255 Leu Lys Thr Val Val Ile Val Leu Gly Ala Phe Ile Ile Cys Trp Thr 260 265 270 Pro Gly Leu Val Leu Leu Leu Leu Asp Val Cys Cys Pro Gln Cys Asp 275 280 285 Val Leu Ala Tyr Glu Lys Phe Phe Leu Leu Leu Ala Glu Phe Asn Ser 290 295 300 Ala Met Asn Pro Ile Ile Tyr Ser Tyr Arg Asp Lys Glu Met Ser Ala 305 310 315 320 Thr Phe Arg Gln Ile Leu Cys Cys Gln Arg Ser Glu Asn Pro Thr Gly 325 330 335 Pro Thr Glu Ser Ser Asp Arg Ser Ala Ser Ser Leu Asn His Thr Ile 340 345 350 Leu Ala Gly Val His Ser Asn Asp His Ser Val Val 355 360 75 2192 DNA Homo Sapiens 75 agtctggccc tggacaaccc cagcaaagcc gccctcagcc agcccagaag cactgggcct 60 tggccacagc aacacccact gagcacgctg ggagctgagt atggcgtccc tggtctcgct 120 ggagctgggg ctgcttctgg ctgtgctggt ggtgacggcg acggcgtccc cgcctgctgg 180 tctgctgagc ctgctcacct ctggccaggg cgctctggat caagaggctc tgggcggcct 240 gttaaatacg ctggcggacc gtgtgcactg caccaacggg ccgtgtggaa agtgcctgtc 300 tgtggaggac gccctgggcc tgggcgagcc tgaggggtca gggctgcccc cgggcccggt 360 cctggaggcc aggtacgtcg cccgcctcag tgccgccgcc gtcctgtacc tcagcaaccc 420 cgagggcacc tgtgaggaca ctcgggctgg cctctgggcc tctcatgcag accacctcct 480 ggccctgctc gagagcccca aggccctgac cccgggcctg agctggctgc tgcagaggat 540 gcaggcccgg gctgccggcc agacccccaa gacggcctgc gtagatatcc ctcagctgct 600 ggaggaggcg gtgggggcgg gggctccggg cagtgctggc ggcgtcctgg ctgccctgct 660 ggaccatgtc aggagcgggt cttgcttcca cgccttgccg agccctcagt acttcgtgga 720 ctttgtgttc cagcagcaca gcagcgaggt ccctatgacg ctggccgagc tgtcagcctt 780 gatgcagcgc ctgggggtgg gcagggaggc ccacagtgac cacagtcatc ggcacagggg 840 agccagcagc cgggaccctg tgcccctcat cagctccagc aacagctcca gtgtgtggga 900 cacggtatgc ctgagtgcca gggacgtgat ggctgcatat ggactgtcgg aacaggctgg 960 ggtgaccccg gaggcctggg cccaactgag ccctgccctg ctccaacagc agctgagtgg 1020 agcctgcacc tcccagtcca ggccccccgt ccaggaccag ctcagccagt cagagaggta 1080 tctgtacggc tccctggcca cgctgctcat ctgcctctgc gcggtctttg gcctcctgct 1140 gctgacctgc actggctgca ggggggtcgc ccactacatc ctgcagacct tcctgagcct 1200 ggcagtgggt gcactcactg gggacgctgt cctgcatctg acgcccaagg tgctggggct 1260 gcatacacac agcgaagagg gcctcagccc acagcccacc tggcgcctcc tggctatgct 1320 ggccgggctc tacgccttct tcctgtttga gaacctcttc aatctcctgc tgcccaggga 1380 cccggaggac ctggaggacg ggccctgcgg ccacagcagc catagccacg ggggccacag 1440 ccacggtgtg tccctgcagc tggcacccag cgagctccgg cagcccaagc ccccccacga 1500 gggctcccgc gcagacctgg tggcggagga gagcccggag ctgctgaacc ctgagcccag 1560 gagactgagc ccagagttga ggctactgcc ctatatgatc actctgggcg acgccgtgca 1620 caacttcgcc gacgggctgg ccgtgggcgc cgccttcgcg tcctcctgga agaccgggct 1680 ggccacctcg ctggccgtgt tctgccacga gttgccacac gagctggggg acttcgccgc 1740 cttgctgcac gcggggctgt ccgtgcgcca agcactgctg ctgaacctgg cctccgcgct 1800 cacggccttc gctggtctct acgtggcact cgcggttgga gtcagcgagg agagcgaggc 1860 ctggatcctg gcagtggcca ccggcctgtt cctctacgta gcactctgcg acatgctccc 1920 ggcgatgttg aaagtacggg acccgcggcc ctggctcctc ttcctgctgc acaacgtggg 1980 cctgctgggc ggctggaccg tcctgctgct gctgtccctg tacgaggatg acatcacctt 2040 76 647 PRT Homo Sapiens 76 Met Ala Ser Leu Val Ser Leu Glu Leu Gly Leu Leu Leu Ala Val Leu 1 5 10 15 Val Val Thr Ala Thr Ala Ser Pro Pro Ala Gly Leu Leu Ser Leu Leu 20 25 30 Thr Ser Gly Gln Gly Ala Leu Asp Gln Glu Ala Leu Gly Gly Leu Leu 35 40 45 Asn Thr Leu Ala Asp Arg Val His Cys Thr Asn Gly Pro Cys Gly Lys 50 55 60 Cys Leu Ser Val Glu Asp Ala Leu Gly Leu Gly Glu Pro Glu Gly Ser 65 70 75 80 Gly Leu Pro Pro Gly Pro Val Leu Glu Ala Arg Tyr Val Ala Arg Leu 85 90 95 Ser Ala Ala Ala Val Leu Tyr Leu Ser Asn Pro Glu Gly Thr Cys Glu 100 105 110 Asp Thr Arg Ala Gly Leu Trp Ala Ser His Ala Asp His Leu Leu Ala 115 120 125 Leu Leu Glu Ser Pro Lys Ala Leu Thr Pro Gly Leu Ser Trp Leu Leu 130 135 140 Gln Arg Met Gln Ala Arg Ala Ala Gly Gln Thr Pro Lys Thr Ala Cys 145 150 155 160 Val Asp Ile Pro Gln Leu Leu Glu Glu Ala Val Gly Ala Gly Ala Pro 165 170 175 Gly Ser Ala Gly Gly Val Leu Ala Ala Leu Leu Asp His Val Arg Ser 180 185 190 Gly Ser Cys Phe His Ala Leu Pro Ser Pro Gln Tyr Phe Val Asp Phe 195 200 205 Val Phe Gln Gln His Ser Ser Glu Val Pro Met Thr Leu Ala Glu Leu 210 215 220 Ser Ala Leu Met Gln Arg Leu Gly Val Gly Arg Glu Ala His Ser Asp 225 230 235 240 His Ser His Arg His Arg Gly Ala Ser Ser Arg Asp Pro Val Pro Leu 245 250 255 Ile Ser Ser Ser Asn Ser Ser Ser Val Trp Asp Thr Val Cys Leu Ser 260 265 270 Ala Arg Asp Val Met Ala Ala Tyr Gly Leu Ser Glu Gln Ala Gly Val 275 280 285 Thr Pro Glu Ala Trp Ala Gln Leu Ser Pro Ala Leu Leu Gln Gln Gln 290 295 300 Leu Ser Gly Ala Cys Thr Ser Gln Ser Arg Pro Pro Val Gln Asp Gln 305 310 315 320 Leu Ser Gln Ser Glu Arg Tyr Leu Tyr Gly Ser Leu Ala Thr Leu Leu 325 330 335 Ile Cys Leu Cys Ala Val Phe Gly Leu Leu Leu Leu Thr Cys Thr Gly 340 345 350 Cys Arg Gly Val Ala His Tyr Ile Leu Gln Thr Phe Leu Ser Leu Ala 355 360 365 Val Gly Ala Leu Thr Gly Asp Ala Val Leu His Leu Thr Pro Lys Val 370 375 380 Leu Gly Leu His Thr His Ser Glu Glu Gly Leu Ser Pro Gln Pro Thr 385 390 395 400 Trp Arg Leu Leu Ala Met Leu Ala Gly Leu Tyr Ala Phe Phe Leu Phe 405 410 415 Glu Asn Leu Phe Asn Leu Leu Leu Pro Arg Asp Pro Glu Asp Leu Glu 420 425 430 Asp Gly Pro Cys Gly His Ser Ser His Ser His Gly Gly His Ser His 435 440 445 Gly Val Ser Leu Gln Leu Ala Pro Ser Glu Leu Arg Gln Pro Lys Pro 450 455 460 Pro His Glu Gly Ser Arg Ala Asp Leu Val Ala Glu Glu Ser Pro Glu 465 470 475 480 Leu Leu Asn Pro Glu Pro Arg Arg Leu Ser Pro Glu Leu Arg Leu Leu 485 490 495 Pro Tyr Met Ile Thr Leu Gly Asp Ala Val His Asn Phe Ala Asp Gly 500 505 510 Leu Ala Val Gly Ala Ala Phe Ala Ser Ser Trp Lys Thr Gly Leu Ala 515 520 525 Thr Ser Leu Ala Val Phe Cys His Glu Leu Pro His Glu Leu Gly Asp 530 535 540 Phe Ala Ala Leu Leu His Ala Gly Leu Ser Val Arg Gln Ala Leu Leu 545 550 555 560 Leu Asn Leu Ala Ser Ala Leu Thr Ala Phe Ala Gly Leu Tyr Val Ala 565 570 575 Leu Ala Val Gly Val Ser Glu Glu Ser Glu Ala Trp Ile Leu Ala Val 580 585 590 Ala Thr Gly Leu Phe Leu Tyr Val Ala Leu Cys Asp Met Leu Pro Ala 595 600 605 Met Leu Lys Val Arg Asp Pro Arg Pro Trp Leu Leu Phe Leu Leu His 610 615 620 Asn Val Gly Leu Leu Gly Gly Trp Thr Val Leu Leu Leu Leu Ser Leu 625 630 635 640 Tyr Glu Asp Asp Ile Thr Phe 645 77 2952 DNA Homo Sapiens 77 aactgatcgc ggcctagtcc cgacgcgtgt gtgctagtga gccggagccg gcgacggcgg 60 cagtggcggc ccggcctgca ggagcccgac ggggtctctg ccatggggga gtgacgcgcc 120 tgcacccgct gttccgcggc agcggcgaga catgaggaga ccccgcgaca ggggcagcgg 180 cggcggctcg tgagccccgg gatggaggag aaatacggcg gggacgtgct ggccggcccc 240 ggcggcggcg gcggccttgg gccggtggac gtacccagcg ctcgattaac aaaatatatt 300 gtgttactat gtttcactaa atttttgaag gctgtgggac ttttcgaatc atatgatctc 360 ctaaaagctg ttcacattgt tcagttcatt tttatattaa aacttgggac tgcatttttt 420 atggttttgt ttcaaaagcc attttcttct gggaaaacta ttaccaaaca ccagtggatc 480 aaaatattta aacatgcagt tgctgggtgt attatttcac tcttgtggtt ttttggcctc 540 actctttgtg gaccactaag gactttgctg ctatttgagc acagtgatat tgttgtcatt 600 tcactactca gtgttttgtt caccagttct ggaggaggac cagcaaagac aaggggagct 660 gcttttttca ttattgctgt gatctgttta ttgctttttg acaatgatga tctcatggct 720 aaaatggctg aacaccctga aggacatcat gacagtgctc taactcatat gctttacaca 780 gccattgcct tcttaggtgt ggcagatcac aagggtggag tattattgct agtactggct 840 ttgtgttgta aagttggttt tcatacagct tccagaaagc tctctgtcga cgttggtgga 900 gctaaacgtc ttcaagcttt atctcatctt gtttctgtgc ttctcttgtg cccatgggtc 960 attgttcttt ctgtgacaac tgagagtaaa gtggagtctt ggttttctct cattatgcct 1020 tttgcaacgg ttatcttttt tgtcatgatc ctggatttct acgtggattc catttgttca 1080 gtcaaaatgg aagtttccaa atgtgctcgt tatggatcct ttcccatttt tattagtgct 1140 ctcctttttg gaaatttttg gacacatcca ataacagacc agcttcgggc tatgaacaaa 1200 gcagcacacc aggagagcac tgaacacgtc ctgtctggag gagtggtagt gagtgctata 1260 ttcttcattt tgtctgccaa tatcttatca tctccctcta agagaggaca aaaaggtacc 1320 cttattggat attctcctga aggaacacct ctttataact tcatgggtga tgcttttcag 1380 catagctctc aatcgatccc taggtttatt aaggaatcac taaaacaaat tcttgaggag 1440 agtgactcta ggcagatctt ttacttcttg tgcttgaatc tgctttttac ctttgtggaa 1500 ttattctatg gcgtgctgac caatagtctg ggcctgatct cggatggatt ccacatgctt 1560 tttgactgct ctgctttagt catgggactt tttgctgccc tgatgagtag gtggaaagcc 1620 actcggattt tctcctatgg gtacggccga atagaaattc tgtctggatt tattaatgga 1680 ctttttctaa tagtaatagc gttttttgtg tttatggagt cagtggctag attgattgat 1740 cctccagaat tagacactca catgttaaca ccagtctcag ttggagggct gatagtaaac 1800 cttattggta tctgtgcctt tagccatgcc catagccatg cccatggagc ttctcaagga 1860 agctgtcact catctgatca cagccattca caccatatgc atggacacag tgaccatggg 1920 catggtcaca gccacggatc tgcgggtgga ggcatgaatg ctaacatgag gggtgtattt 1980 ctacatgttt tggcagatac tcttggcagc attggtgtga tcgtatccac agttcttata 2040 gagcagtttg gatggttcat cgctgaccca ctctgttctc tttttattgc tatattaata 2100 tttctcagtg ttgttccact gattaaagat gcctgccagg ttctactcct gagattgcca 2160 ccagaatatg aaaaagaact acatattgct ttagaaaaga tacagaaaat tgaaggatta 2220 atatcatacc gagaccctca tttttggcgt cattctgcta gtattgtggc aggaacaatt 2280 catatacagg tgacatctga tgtgctagaa caaagaatag tacagcaggt tacaggaata 2340 cttaaagatg ctggagtaaa caatttaaca attcaagtgg aaaaggaggc atactttcaa 2400 catatgtctg gcctaagtac tggatttcat gatgttctgg ctatgacaaa acaaatggaa 2460 tccatgaaat actgcaaaga tggtacttac atcatgtgag ataactcaag aattacccct 2520 ggagaataaa caatgaagat taaatgactc agtatttgta atattgccag aaggataaaa 2580 attacacatt aactgtacag aaacagagtt ccctactact ggatcaagga atctttcttg 2640 aaggaaattt aaatacagaa tgaaacatta atggtaaaag tggagtaatt atttaaatta 2700 tgtgtataaa aggaatcaaa ttttgagtaa acatgatgta ttacatcatc ttcgaaaata 2760 gatatgatgg attctagtga agaccaaaat tacttctgtt tactttctat caggaagcat 2820 ctccattgta aatatgtatt tacatgttta ttacaaagac ccaaatgaaa aatttttagt 2880 ccattttttg catagcctaa agataaaata ggaataaaag ttctatattt atggaaaaaa 2940 aaaaaaaaaa aa 2952 78 765 PRT Homo Sapiens 78 Met Glu Glu Lys Tyr Gly Gly Asp Val Leu Ala Gly Pro Gly Gly Gly 1 5 10 15 Gly Gly Leu Gly Pro Val Asp Val Pro Ser Ala Arg Leu Thr Lys Tyr 20 25 30 Ile Val Leu Leu Cys Phe Thr Lys Phe Leu Lys Ala Val Gly Leu Phe 35 40 45 Glu Ser Tyr Asp Leu Leu Lys Ala Val His Ile Val Gln Phe Ile Phe 50 55 60 Ile Leu Lys Leu Gly Thr Ala Phe Phe Met Val Leu Phe Gln Lys Pro 65 70 75 80 Phe Ser Ser Gly Lys Thr Ile Thr Lys His Gln Trp Ile Lys Ile Phe 85 90 95 Lys His Ala Val Ala Gly Cys Ile Ile Ser Leu Leu Trp Phe Phe Gly 100 105 110 Leu Thr Leu Cys Gly Pro Leu Arg Thr Leu Leu Leu Phe Glu His Ser 115 120 125 Asp Ile Val Val Ile Ser Leu Leu Ser Val Leu Phe Thr Ser Ser Gly 130 135 140 Gly Gly Pro Ala Lys Thr Arg Gly Ala Ala Phe Phe Ile Ile Ala Val 145 150 155 160 Ile Cys Leu Leu Leu Phe Asp Asn Asp Asp Leu Met Ala Lys Met Ala 165 170 175 Glu His Pro Glu Gly His His Asp Ser Ala Leu Thr His Met Leu Tyr 180 185 190 Thr Ala Ile Ala Phe Leu Gly Val Ala Asp His Lys Gly Gly Val Leu 195 200 205 Leu Leu Val Leu Ala Leu Cys Cys Lys Val Gly Phe His Thr Ala Ser 210 215 220 Arg Lys Leu Ser Val Asp Val Gly Gly Ala Lys Arg Leu Gln Ala Leu 225 230 235 240 Ser His Leu Val Ser Val Leu Leu Leu Cys Pro Trp Val Ile Val Leu 245 250 255 Ser Val Thr Thr Glu Ser Lys Val Glu Ser Trp Phe Ser Leu Ile Met 260 265 270 Pro Phe Ala Thr Val Ile Phe Phe Val Met Ile Leu Asp Phe Tyr Val 275 280 285 Asp Ser Ile Cys Ser Val Lys Met Glu Val Ser Lys Cys Ala Arg Tyr 290 295 300 Gly Ser Phe Pro Ile Phe Ile Ser Ala Leu Leu Phe Gly Asn Phe Trp 305 310 315 320 Thr His Pro Ile Thr Asp Gln Leu Arg Ala Met Asn Lys Ala Ala His 325 330 335 Gln Glu Ser Thr Glu His Val Leu Ser Gly Gly Val Val Val Ser Ala 340 345 350 Ile Phe Phe Ile Leu Ser Ala Asn Ile Leu Ser Ser Pro Ser Lys Arg 355 360 365 Gly Gln Lys Gly Thr Leu Ile Gly Tyr Ser Pro Glu Gly Thr Pro Leu 370 375 380 Tyr Asn Phe Met Gly Asp Ala Phe Gln His Ser Ser Gln Ser Ile Pro 385 390 395 400 Arg Phe Ile Lys Glu Ser Leu Lys Gln Ile Leu Glu Glu Ser Asp Ser 405 410 415 Arg Gln Ile Phe Tyr Phe Leu Cys Leu Asn Leu Leu Phe Thr Phe Val 420 425 430 Glu Leu Phe Tyr Gly Val Leu Thr Asn Ser Leu Gly Leu Ile Ser Asp 435 440 445 Gly Phe His Met Leu Phe Asp Cys Ser Ala Leu Val Met Gly Leu Phe 450 455 460 Ala Ala Leu Met Ser Arg Trp Lys Ala Thr Arg Ile Phe Ser Tyr Gly 465 470 475 480 Tyr Gly Arg Ile Glu Ile Leu Ser Gly Phe Ile Asn Gly Leu Phe Leu 485 490 495 Ile Val Ile Ala Phe Phe Val Phe Met Glu Ser Val Ala Arg Leu Ile 500 505 510 Asp Pro Pro Glu Leu Asp Thr His Met Leu Thr Pro Val Ser Val Gly 515 520 525 Gly Leu Ile Val Asn Leu Ile Gly Ile Cys Ala Phe Ser His Ala His 530 535 540 Ser His Ala His Gly Ala Ser Gln Gly Ser Cys His Ser Ser Asp His 545 550 555 560 Ser His Ser His His Met His Gly His Ser Asp His Gly His Gly His 565 570 575 Ser His Gly Ser Ala Gly Gly Gly Met Asn Ala Asn Met Arg Gly Val 580 585 590 Phe Leu His Val Leu Ala Asp Thr Leu Gly Ser Ile Gly Val Ile Val 595 600 605 Ser Thr Val Leu Ile Glu Gln Phe Gly Trp Phe Ile Ala Asp Pro Leu 610 615 620 Cys Ser Leu Phe Ile Ala Ile Leu Ile Phe Leu Ser Val Val Pro Leu 625 630 635 640 Ile Lys Asp Ala Cys Gln Val Leu Leu Leu Arg Leu Pro Pro Glu Tyr 645 650 655 Glu Lys Glu Leu His Ile Ala Leu Glu Lys Ile Gln Lys Ile Glu Gly 660 665 670 Leu Ile Ser Tyr Arg Asp Pro His Phe Trp Arg His Ser Ala Ser Ile 675 680 685 Val Ala Gly Thr Ile His Ile Gln Val Thr Ser Asp Val Leu Glu Gln 690 695 700 Arg Ile Val Gln Gln Val Thr Gly Ile Leu Lys Asp Ala Gly Val Asn 705 710 715 720 Asn Leu Thr Ile Gln Val Glu Lys Glu Ala Tyr Phe Gln His Met Ser 725 730 735 Gly Leu Ser Thr Gly Phe His Asp Val Leu Ala Met Thr Lys Gln Met 740 745 750 Glu Ser Met Lys Tyr Cys Lys Asp Gly Thr Tyr Ile Met 755 760 765 79 2074 DNA Homo Sapiens 79 cacaaggcgg tagccatggc ggaggcggcg gctgcagcgg gtgggactgg cttgggcgcg 60 ggcgcgagct acgggtctgc agcggaccgg gaccgggacc cggacccgga ccgcgccggg 120 cggaggctgc gggttctctc tggccatctg ctgggccggc cccgggaggc tctgagtacc 180 aatgagtgca aagcgcggag agccgcgtcg gcggccacgg cagcgcccac ggccactccc 240 gccgcgcagg agtcgggcac catcccaaag aagcggcaag aagttatgaa atggaatgga 300 tggggatata atgattctaa attcatcttc aataagaagg gccaaattga attgactggg 360 aaaaggtacc ctcttagtgg catgggttta ccaacattta aagaatggat ccaaaatacc 420 cttggagtaa atgtggagca taaaactacc tctaaagcat ccttaaatcc tagtgataca 480 cctccttctg ttgtaaatga agattttctt catgacctta aagaaactaa tatttcatat 540 tcacaagagg cagatgatcg agtatttaga gctcatggtc attgtcttca tgagatattt 600 ttgctcaggg aaggaatgtt tgagcgaatt cctgatatag ttttatggcc aacatgccat 660 gatgatgtag ttaagattgt gaatctagct tgcaaatata atctttgtat cataccaatt 720 ggtggaggaa caagtgtttc atatggcctg atgtgtcctg cagatgagac aagaacaatt 780 atttctttgg acacttcaca aatgaatcga attctctggg ttgatgagaa caatttgaca 840 gctcatgtgg aggctggcat aacaggacaa gagttggaaa gacagcttaa agaaagtggt 900 tattgtacag gtcatgaacc agattccctg gagttcagta ctgtaggagg atgggtatct 960 actcgcgcat caggcatgaa gaagaatatc tatggcaata tcgaggacct ggtggttcat 1020 ataaaaatgg taacacctag aggtataata gaaaaaagct gtcaaggacc tcgtatgtca 1080 acaggccctg atatccatca cttcatcatg ggatctgaag gaactcttgg tgtaataaca 1140 gaagctacaa taaaaatcag accagtccct gaataccaaa agtatggctc agtagctttc 1200 cctaattttg aacaaggagt agcctgttta agagaaattg caaaacagag atgtgctccg 1260 gcatctattc gcctcatgga caacaagcag tttcagtttg gtcatgctct taaacctcag 1320 gtttcctcta tctttacatc atttttggac ggattaaaaa agttttatat tacaaagttt 1380 aaaggatttg acccaaatca gctaagtgta gccacattac tgtttgaggg ggatcgtgag 1440 aaggttcttc aacatgaaaa acaagtgtat gatattgctg caaaatttgg tgggttggca 1500 gctggagaag ataatggaca gagaggttat ttgctgacct atgttattgc atacattcga 1560 gacttggctt tggaatacta tgtattagga gaatcttttg agacttctgc tccttgggac 1620 agggtggtag atctctgtag aaatgtaaaa gaaagaataa caagggaatg caaagagaag 1680 ggtgttcagt ttgctccttt ttctacatgc agggtgacgc agacttacga tgcaggtgct 1740 tgtatctact tctattttgc ctttaactac aggggaatta gtgacccact gaccgtattt 1800 gaacaaactg aggcagctgc tagagaagaa atccttgcta atggagggag cctgtcacat 1860 caccatggag tgggcaagtt acggaagcaa tggctaaagg aaagtatctc tgatgtcggc 1920 tttgggatgc tgaagtctgt caaggaatat gtggacccca ataacatctt tggaaacaga 1980 aaccttttat aaatccatta gtaccattac aaaaaaatgt caattttttt tttaagtttt 2040 caactgtggt tatactagta atcaaatata tcat 2074 80 658 PRT Homo Sapiens 80 Met Ala Glu Ala Ala Ala Ala Ala Gly Gly Thr Gly Leu Gly Ala Gly 1 5 10 15 Ala Ser Tyr Gly Ser Ala Ala Asp Arg Asp Arg Asp Pro Asp Pro Asp 20 25 30 Arg Ala Gly Arg Arg Leu Arg Val Leu Ser Gly His Leu Leu Gly Arg 35 40 45 Pro Arg Glu Ala Leu Ser Thr Asn Glu Cys Lys Ala Arg Arg Ala Ala 50 55 60 Ser Ala Ala Thr Ala Ala Pro Thr Ala Thr Pro Ala Ala Gln Glu Ser 65 70 75 80 Gly Thr Ile Pro Lys Lys Arg Gln Glu Val Met Lys Trp Asn Gly Trp 85 90 95 Gly Tyr Asn Asp Ser Lys Phe Ile Phe Asn Lys Lys Gly Gln Ile Glu 100 105 110 Leu Thr Gly Lys Arg Tyr Pro Leu Ser Gly Met Gly Leu Pro Thr Phe 115 120 125 Lys Glu Trp Ile Gln Asn Thr Leu Gly Val Asn Val Glu His Lys Thr 130 135 140 Thr Ser Lys Ala Ser Leu Asn Pro Ser Asp Thr Pro Pro Ser Val Val 145 150 155 160 Asn Glu Asp Phe Leu His Asp Leu Lys Glu Thr Asn Ile Ser Tyr Ser 165 170 175 Gln Glu Ala Asp Asp Arg Val Phe Arg Ala His Gly His Cys Leu His 180 185 190 Glu Ile Phe Leu Leu Arg Glu Gly Met Phe Glu Arg Ile Pro Asp Ile 195 200 205 Val Leu Trp Pro Thr Cys His Asp Asp Val Val Lys Ile Val Asn Leu 210 215 220 Ala Cys Lys Tyr Asn Leu Cys Ile Ile Pro Ile Gly Gly Gly Thr Ser 225 230 235 240 Val Ser Tyr Gly Leu Met Cys Pro Ala Asp Glu Thr Arg Thr Ile Ile 245 250 255 Ser Leu Asp Thr Ser Gln Met Asn Arg Ile Leu Trp Val Asp Glu Asn 260 265 270 Asn Leu Thr Ala His Val Glu Ala Gly Ile Thr Gly Gln Glu Leu Glu 275 280 285 Arg Gln Leu Lys Glu Ser Gly Tyr Cys Thr Gly His Glu Pro Asp Ser 290 295 300 Leu Glu Phe Ser Thr Val Gly Gly Trp Val Ser Thr Arg Ala Ser Gly 305 310 315 320 Met Lys Lys Asn Ile Tyr Gly Asn Ile Glu Asp Leu Val Val His Ile 325 330 335 Lys Met Val Thr Pro Arg Gly Ile Ile Glu Lys Ser Cys Gln Gly Pro 340 345 350 Arg Met Ser Thr Gly Pro Asp Ile His His Phe Ile Met Gly Ser Glu 355 360 365 Gly Thr Leu Gly Val Ile Thr Glu Ala Thr Ile Lys Ile Arg Pro Val 370 375 380 Pro Glu Tyr Gln Lys Tyr Gly Ser Val Ala Phe Pro Asn Phe Glu Gln 385 390 395 400 Gly Val Ala Cys Leu Arg Glu Ile Ala Lys Gln Arg Cys Ala Pro Ala 405 410 415 Ser Ile Arg Leu Met Asp Asn Lys Gln Phe Gln Phe Gly His Ala Leu 420 425 430 Lys Pro Gln Val Ser Ser Ile Phe Thr Ser Phe Leu Asp Gly Leu Lys 435 440 445 Lys Phe Tyr Ile Thr Lys Phe Lys Gly Phe Asp Pro Asn Gln Leu Ser 450 455 460 Val Ala Thr Leu Leu Phe Glu Gly Asp Arg Glu Lys Val Leu Gln His 465 470 475 480 Glu Lys Gln Val Tyr Asp Ile Ala Ala Lys Phe Gly Gly Leu Ala Ala 485 490 495 Gly Glu Asp Asn Gly Gln Arg Gly Tyr Leu Leu Thr Tyr Val Ile Ala 500 505 510 Tyr Ile Arg Asp Leu Ala Leu Glu Tyr Tyr Val Leu Gly Glu Ser Phe 515 520 525 Glu Thr Ser Ala Pro Trp Asp Arg Val Val Asp Leu Cys Arg Asn Val 530 535 540 Lys Glu Arg Ile Thr Arg Glu Cys Lys Glu Lys Gly Val Gln Phe Ala 545 550 555 560 Pro Phe Ser Thr Cys Arg Val Thr Gln Thr Tyr Asp Ala Gly Ala Cys 565 570 575 Ile Tyr Phe Tyr Phe Ala Phe Asn Tyr Arg Gly Ile Ser Asp Pro Leu 580 585 590 Thr Val Phe Glu Gln Thr Glu Ala Ala Ala Arg Glu Glu Ile Leu Ala 595 600 605 Asn Gly Gly Ser Leu Ser His His His Gly Val Gly Lys Leu Arg Lys 610 615 620 Gln Trp Leu Lys Glu Ser Ile Ser Asp Val Gly Phe Gly Met Leu Lys 625 630 635 640 Ser Val Lys Glu Tyr Val Asp Pro Asn Asn Ile Phe Gly Asn Arg Asn 645 650 655 Leu Leu 81 1753 DNA Homo Sapiens 81 ctgcacgaga ggcacagatt tatcaagctc ctcagtcaac aaacacatca ccggaagaaa 60 catggaagga aaggaatttt aaaaggaaat accaatctct gtgcaaacaa agccttgtat 120 attcatgttt gcaccaatct actgtgagat ttatgaagaa aaacaaattg cggacaactc 180 tctatgtaca cttacaaatg cctcagttga tgcttgtggg ctgtttgtca gcgttctgtg 240 ataatgaaca catggacttc tgtttattaa attcagttga cccctttagc caattgccag 300 gagcctggat ttttacttcc aactgctgat atctgtgtaa aaattgatct acatccaccc 360 tttaaaagca ttgatgaatt aattagaact ttagacaaca agaaaaattg aaaagaattc 420 tcagtaaaag cgaattcgat gttcaaaaca aactacaaag agacaagact tctctgttta 480 ctttctaaga actaatataa ttgctacctt aaaaaggaaa aaatgaacag cacatgtatt 540 gaagaacagc atgacctgga tcactatttg tttcccattg tttacatctt tgtgattata 600 gtcagcattc cagccaatat tggatctctg tgtgtgtctt tcctgcaacc caagaaggaa 660 agtgaactag gaatttacct cttcagtttg tcactatcag atttactcta tgcattaact 720 ctccctttat ggattgatta tacttggaat aaagacaact ggactttctc tcctgccttg 780 tgcaaaggga gtgcttttct catgtacatg aagttttaca gcagcacagc attcctcacc 840 tgcattgccg ttgatcggta tttggctgtt gtctaccctt tgaagttttt tttcctaagg 900 acaagaagaa ttgcactcat ggtcagcctg tccatctgga tattggaaac catcttcaat 960 gctgtcatgt tgtgggaaga tgaaacagtt gttgaatatt gcgatgccga aaagtctaat 1020 tttactttat gctatgacaa atacccttta gagaaatggc aaatcaacct caacttgttc 1080 aggacgtgta caggctatgc aatacctttg gtcaccatcc tgatctgtaa ccggaaagtc 1140 taccaagctg tgcggcacaa taaagccacg gaaaacaagg aaaagaagag aatcataaaa 1200 ctacttgtca gcatcacagt tacttttgtc ttatgcttta ctccctttca tgtgatgttg 1260 ctgattcgct gcattttaga gcatgctgtg aacttcgaag accacagcaa ttctgggaag 1320 cgaacttaca caatgtatag aatcacggtt gcattaacaa gtttaaattg tgttgctgat 1380 ccaattctgt actgttttgt taccgaaaca ggaagatatg atatgtggaa tatattaaaa 1440 ttctgcactg ggaggtgtaa tacatcacaa agacaaagaa aacgcatact ttctgtgtct 1500 acaaaagata ctatggaatt agaggtcctt gagtagaacc aaggatgttt tgaagggaag 1560 ggaagtttaa gttatgcatt attatatcat caagattaca ttttgaaaag gaaatctagc 1620 atgtgagggg actaagtgtt ctcagagtga tgttttaatc cagtccaata aaaatatctt 1680 aaaactgcat tgtacagctc cctccctgcg ttttattaaa tgatgtatat taaacaaaga 1740 tcaatatttt ctt 1753 82 337 PRT Homo Sapiens 82 Met Asn Ser Thr Cys Ile Glu Glu Gln His Asp Leu Asp His Tyr Leu 1 5 10 15 Phe Pro Ile Val Tyr Ile Phe Val Ile Ile Val Ser Ile Pro Ala Asn 20 25 30 Ile Gly Ser Leu Cys Val Ser Phe Leu Gln Pro Lys Lys Glu Ser Glu 35 40 45 Leu Gly Ile Tyr Leu Phe Ser Leu Ser Leu Ser Asp Leu Leu Tyr Ala 50 55 60 Leu Thr Leu Pro Leu Trp Ile Asp Tyr Thr Trp Asn Lys Asp Asn Trp 65 70 75 80 Thr Phe Ser Pro Ala Leu Cys Lys Gly Ser Ala Phe Leu Met Tyr Met 85 90 95 Lys Phe Tyr Ser Ser Thr Ala Phe Leu Thr Cys Ile Ala Val Asp Arg 100 105 110 Tyr Leu Ala Val Val Tyr Pro Leu Lys Phe Phe Phe Leu Arg Thr Arg 115 120 125 Arg Ile Ala Leu Met Val Ser Leu Ser Ile Trp Ile Leu Glu Thr Ile 130 135 140 Phe Asn Ala Val Met Leu Trp Glu Asp Glu Thr Val Val Glu Tyr Cys 145 150 155 160 Asp Ala Glu Lys Ser Asn Phe Thr Leu Cys Tyr Asp Lys Tyr Pro Leu 165 170 175 Glu Lys Trp Gln Ile Asn Leu Asn Leu Phe Arg Thr Cys Thr Gly Tyr 180 185 190 Ala Ile Pro Leu Val Thr Ile Leu Ile Cys Asn Arg Lys Val Tyr Gln 195 200 205 Ala Val Arg His Asn Lys Ala Thr Glu Asn Lys Glu Lys Lys Arg Ile 210 215 220 Ile Lys Leu Leu Val Ser Ile Thr Val Thr Phe Val Leu Cys Phe Thr 225 230 235 240 Pro Phe His Val Met Leu Leu Ile Arg Cys Ile Leu Glu His Ala Val 245 250 255 Asn Phe Glu Asp His Ser Asn Ser Gly Lys Arg Thr Tyr Thr Met Tyr 260 265 270 Arg Ile Thr Val Ala Leu Thr Ser Leu Asn Cys Val Ala Asp Pro Ile 275 280 285 Leu Tyr Cys Phe Val Thr Glu Thr Gly Arg Tyr Asp Met Trp Asn Ile 290 295 300 Leu Lys Phe Cys Thr Gly Arg Cys Asn Thr Ser Gln Arg Gln Arg Lys 305 310 315 320 Arg Ile Leu Ser Val Ser Thr Lys Asp Thr Met Glu Leu Glu Val Leu 325 330 335 Glu 83 1053 DNA Homo Sapiens 83 atggagctgg cggtcgggaa cctcagcgag ggcaacgcga gctgtccgga gccccccgcc 60 ccggagcccg ggccgctgtt cggcatcggc gtggagaact tcgtcacgct ggtggtgttc 120 ggcctgatct tcgcgctggg cgtgctgggc aacagcctag tgatcaccgt gctggcgcgc 180 agcaagccgg gcaagccgcg gagcaccacc aacctgttca tcctcaacct gagcatcgcc 240 gacctggcct acctgctctt ctgcatcccc ttccaggcca ccgtgtacgc gctgcccacc 300 tgggtgctgg gcgccttcat ctgcaagttc atccactact tcttcaccgt gtccatgctg 360 gtgagcatct tcaccctggc cgcgatgtcc gtggaccgct acgtggccat cgtgcactcg 420 cggcgctcct cctccctcag ggtgtcccgc aacgcgctgc tgggcgtggg ctgcatctgg 480 gcgctgtcca ttgccatggc ctcgcccgtg gcctaccacc agggcctctt ccacccgcgc 540 gccagcaacc agaccttctg ctgggagcag tggcccgacc ctcgccacaa gaaggcctac 600 gtggtgtgca ccttcgtctt cggctacctg ctgccgctcc tgctcatctg cttctgctat 660 gccaaggtcc ttaatcactt gcataaaaag ttgaagaaca tgtcaaagaa gtctgaagca 720 tccaagaaaa agactgcaca gacagttctg gtggtggttg tggtgtttgg aatctcctgg 780 ctgccgcacc acatcatcca tctctgggct gagtttggag ttttcccgct gacgccggct 840 tccttcctct tcagaatcac cgcccactgc ctggcgtaca gcaattcctc cgtgaatcct 900 atcatttatg catttctctc tgaaaatttc aggaaggcct ataaacaagt gttcaagtgt 960 cacattcgca aagattcaca cctgagtgat actaaagaaa ataaaagtcg aatagacacc 1020 ccaccatcaa ccaattgtac tcatgtgtga taa 1053 84 349 PRT Homo Sapiens 84 Met Glu Leu Ala Val Gly Asn Leu Ser Glu Gly Asn Ala Ser Cys Pro 1 5 10 15 Glu Pro Pro Ala Pro Glu Pro Gly Pro Leu Phe Gly Ile Gly Val Glu 20 25 30 Asn Phe Val Thr Leu Val Val Phe Gly Leu Ile Phe Ala Leu Gly Val 35 40 45 Leu Gly Asn Ser Leu Val Ile Thr Val Leu Ala Arg Ser Lys Pro Gly 50 55 60 Lys Pro Arg Ser Thr Thr Asn Leu Phe Ile Leu Asn Leu Ser Ile Ala 65 70 75 80 Asp Leu Ala Tyr Leu Leu Phe Cys Ile Pro Phe Gln Ala Thr Val Tyr 85 90 95 Ala Leu Pro Thr Trp Val Leu Gly Ala Phe Ile Cys Lys Phe Ile His 100 105 110 Tyr Phe Phe Thr Val Ser Met Leu Val Ser Ile Phe Thr Leu Ala Ala 115 120 125 Met Ser Val Asp Arg Tyr Val Ala Ile Val His Ser Arg Arg Ser Ser 130 135 140 Ser Leu Arg Val Ser Arg Asn Ala Leu Leu Gly Val Gly Cys Ile Trp 145 150 155 160 Ala Leu Ser Ile Ala Met Ala Ser Pro Val Ala Tyr His Gln Gly Leu 165 170 175 Phe His Pro Arg Ala Ser Asn Gln Thr Phe Cys Trp Glu Gln Trp Pro 180 185 190 Asp Pro Arg His Lys Lys Ala Tyr Val Val Cys Thr Phe Val Phe Gly 195 200 205 Tyr Leu Leu Pro Leu Leu Leu Ile Cys Phe Cys Tyr Ala Lys Val Leu 210 215 220 Asn His Leu His Lys Lys Leu Lys Asn Met Ser Lys Lys Ser Glu Ala 225 230 235 240 Ser Lys Lys Lys Thr Ala Gln Thr Val Leu Val Val Val Val Val Phe 245 250 255 Gly Ile Ser Trp Leu Pro His His Ile Ile His Leu Trp Ala Glu Phe 260 265 270 Gly Val Phe Pro Leu Thr Pro Ala Ser Phe Leu Phe Arg Ile Thr Ala 275 280 285 His Cys Leu Ala Tyr Ser Asn Ser Ser Val Asn Pro Ile Ile Tyr Ala 290 295 300 Phe Leu Ser Glu Asn Phe Arg Lys Ala Tyr Lys Gln Val Phe Lys Cys 305 310 315 320 His Ile Arg Lys Asp Ser His Leu Ser Asp Thr Lys Glu Asn Lys Ser 325 330 335 Arg Ile Asp Thr Pro Pro Ser Thr Asn Cys Thr His Val 340 345 85 3321 DNA Homo Sapiens 85 tgctgtgttg caagaataaa ctttgggtct tggattgcaa taccacctgt ggagaaaatg 60 gtatgcgagg gaaagcgatc agcctcttgc ccttgtttct tcctcttgac cgccaagttc 120 tactggatcc tcacaatgat gcaaagaact cacagccagg agtatgccca ttccatacgg 180 gtggatgggg acattatttt ggggggtctc ttccctgtcc acgcaaaggg agagagaggg 240 gtgccttgtg gggagctgaa gaaggaaaag gggattcaca gactggaggc catgctttat 300 gcaattgacc agattaacaa ggaccctgat ctcctttcca acatcactct gggtgtccgc 360 atcctcgaca cgtgctctag ggacacctat gctttggagc agtctctaac attcgtgcag 420 gcattaatag agaaagatgc ttcggatgtg aagtgtgcta atggagatcc acccattttc 480 accaagcccg acaagatttc tggcgtcata ggtgctgcag caagctccgt gtccatcatg 540 gttgctaaca ttttaagact ttttaagata cctcaaatca gctatgcatc cacagcccca 600 gagctaagtg ataacaccag gtatgacttt ttctctcgag tggttccgcc tgactcctac 660 caagcccaag ccatggtgga catcgtgaca gcactgggat ggaattatgt ttcgacactg 720 gcttctgagg ggaactatgg tgagagcggt gtggaggcct tcacccagat ctcgagggag 780 attggtggtg tttgcattgc tcagtcacag aaaatcccac gtgaaccaag acctggagaa 840 tttgaaaaaa ttatcaaacg cctgctagaa acacctaatg ctcgagcagt gattatgttt 900 gccaatgagg atgacatcag gaggatattg gaagcagcaa aaaaactaaa ccaaagtggg 960 cattttctct ggattggctc agatagttgg ggatccaaaa tagcacctgt ctatcagcaa 1020 gaggagattg cagaaggggc tgtgacaatt ttgcccaaac gagcatcaat tgatggattt 1080 gatcgatact ttagaagccg aactcttgcc aataatcgaa gaaatgtgtg gtttgcagaa 1140 ttctgggagg agaattttgg ctgcaagtta ggatcacatg ggaaaaggaa cagtcatata 1200 aagaaatgca cagggctgga gcgaattgct cgggattcat cttatgaaca ggaaggaaag 1260 gtccaatttg taattgatgc tgtatattcc atggcttacg ccctgcacaa tatgcacaaa 1320 gatctctgcc ctggatacat tggcctttgt ccacgaatga gtaccattga tgggaaagag 1380 ctacttggtt atattcgggc tgtaaatttt aatggcagtg ctggcactcc tgtcactttt 1440 aatgaaaacg gagatgctcc tggacgttat gatatcttcc agtatcaaat aaccaacaaa 1500 agcacagagt acaaagtcat cggccactgg accaatcagc ttcatctaaa agtggaagac 1560 atgcagtggg ctcatagaga acatactcac ccggcgtctg tctgcagcct gccgtgtaag 1620 ccaggggaga ggaagaaaac ggtgaaaggg gtcccttgct gctggcactg tgaacgctgt 1680 gaaggttaca actaccaggt ggatgagctg tcctgtgaac tttgccctct ggatcagaga 1740 cccaacatga accgcacagg ctgccagctt atccccatca tcaaattgga gtggcattct 1800 ccctgggctg tggtgcctgt gtttgttgca atattgggaa tcatcgccac cacctttgtg 1860 atcgtgacct ttgtccgcta taatgacaca cctatcgtga gggcttcagg acgcgaactt 1920 agttacgtgc tcctaacggg gatttttctc tgttattcaa tcacgttttt aatgattgca 1980 gcaccagata caatcatatg ctccttccga cgggtcttcc taggacttgg catgtgtttc 2040 agctatgcag cccttctgac caaaacaaac cgtatccacc gaatatttga gcaggggaag 2100 aaatctgtca cagcgcccaa gttcattagt ccagcatctc agctggtgat caccttcagc 2160 ctcatctccg tccagctcct tggagtgttt gtctggtttg ttgtggatcc cccccacatc 2220 atcattgact atggagagca gcggacacta gatccagaga aggccagggg agtgctcaag 2280 tgtgacattt ctgatctctc actcatttgt tcacttggat acagtatcct cttgatggtc 2340 acttgtactg tttatgccaa taaaacgaga ggtgtcccag agactttcaa tgaagccaaa 2400 cctattggat ttaccatgta taccacctgc atcatttggt tagctttcat ccccatcttt 2460 tttggtacag cccagtcagc agaaaagatg tacatccaga caacaacact tactgtctcc 2520 atgagtttaa gtgcttcagt atctctgggc atgctctata tgcccaaggt ttatattata 2580 atttttcatc cagaacagaa tgttcaaaaa cgcaagagga gcttcaaggc tgtggtgaca 2640 gctgccacca tgcaaagcaa actgatccaa aaaggaaatg acagaccaaa tggcgaggtg 2700 aaaagtgaac tctgtgagag tcttgaaacc aacacttcct ctaccaagac aacatatatc 2760 agttacagca atcattcaat ctgaaacagg gaaatggcac aatctgaaga gacgtggtat 2820 atgatcttaa atgatgaaca tgagaccgca aaaattcact cctggagatc tccgtagact 2880 acaatcaatc aaatcaatag tcagtcttgt aaggaacaaa aattagccat gagccaaaag 2940 tatcaataaa cggggagtga agaaacccgt tttatacaat aaaaccaatg agtgtcaagc 3000 taaagtattg cttattcatg agcagttaaa acaaatcaca aaaggaaaac taatgttagc 3060 tcgtgaaaaa aatgctgttg aaataaataa tgtctgatgt tattcttgta tttttctgtg 3120 attgtgagaa ctcccgttcc tgtcccacat tgtttaactt gtataagaca atgagtctgt 3180 ttcttgtaat ggctgaccag attgaagccc tgggttgtgc taaaaataaa tgcaatgatt 3240 gatgcatgca attttttata caaataattt atttctaata ataaaggaat gttttgcaaa 3300 aaaaaaaaaa aaaaactcga g 3321 86 908 PRT Homo Sapiens 86 Met Val Cys Glu Gly Lys Arg Ser Ala Ser Cys Pro Cys Phe Phe Leu 1 5 10 15 Leu Thr Ala Lys Phe Tyr Trp Ile Leu Thr Met Met Gln Arg Thr His 20 25 30 Ser Gln Glu Tyr Ala His Ser Ile Arg Val Asp Gly Asp Ile Ile Leu 35 40 45 Gly Gly Leu Phe Pro Val His Ala Lys Gly Glu Arg Gly Val Pro Cys 50 55 60 Gly Glu Leu Lys Lys Glu Lys Gly Ile His Arg Leu Glu Ala Met Leu 65 70 75 80 Tyr Ala Ile Asp Gln Ile Asn Lys Asp Pro Asp Leu Leu Ser Asn Ile 85 90 95 Thr Leu Gly Val Arg Ile Leu Asp Thr Cys Ser Arg Asp Thr Tyr Ala 100 105 110 Leu Glu Gln Ser Leu Thr Phe Val Gln Ala Leu Ile Glu Lys Asp Ala 115 120 125 Ser Asp Val Lys Cys Ala Asn Gly Asp Pro Pro Ile Phe Thr Lys Pro 130 135 140 Asp Lys Ile Ser Gly Val Ile Gly Ala Ala Ala Ser Ser Val Ser Ile 145 150 155 160 Met Val Ala Asn Ile Leu Arg Leu Phe Lys Ile Pro Gln Ile Ser Tyr 165 170 175 Ala Ser Thr Ala Pro Glu Leu Ser Asp Asn Thr Arg Tyr Asp Phe Phe 180 185 190 Ser Arg Val Val Pro Pro Asp Ser Tyr Gln Ala Gln Ala Met Val Asp 195 200 205 Ile Val Thr Ala Leu Gly Trp Asn Tyr Val Ser Thr Leu Ala Ser Glu 210 215 220 Gly Asn Tyr Gly Glu Ser Gly Val Glu Ala Phe Thr Gln Ile Ser Arg 225 230 235 240 Glu Ile Gly Gly Val Cys Ile Ala Gln Ser Gln Lys Ile Pro Arg Glu 245 250 255 Pro Arg Pro Gly Glu Phe Glu Lys Ile Ile Lys Arg Leu Leu Glu Thr 260 265 270 Pro Asn Ala Arg Ala Val Ile Met Phe Ala Asn Glu Asp Asp Ile Arg 275 280 285 Arg Ile Leu Glu Ala Ala Lys Lys Leu Asn Gln Ser Gly His Phe Leu 290 295 300 Trp Ile Gly Ser Asp Ser Trp Gly Ser Lys Ile Ala Pro Val Tyr Gln 305 310 315 320 Gln Glu Glu Ile Ala Glu Gly Ala Val Thr Ile Leu Pro Lys Arg Ala 325 330 335 Ser Ile Asp Gly Phe Asp Arg Tyr Phe Arg Ser Arg Thr Leu Ala Asn 340 345 350 Asn Arg Arg Asn Val Trp Phe Ala Glu Phe Trp Glu Glu Asn Phe Gly 355 360 365 Cys Lys Leu Gly Ser His Gly Lys Arg Asn Ser His Ile Lys Lys Cys 370 375 380 Thr Gly Leu Glu Arg Ile Ala Arg Asp Ser Ser Tyr Glu Gln Glu Gly 385 390 395 400 Lys Val Gln Phe Val Ile Asp Ala Val Tyr Ser Met Ala Tyr Ala Leu 405 410 415 His Asn Met His Lys Asp Leu Cys Pro Gly Tyr Ile Gly Leu Cys Pro 420 425 430 Arg Met Ser Thr Ile Asp Gly Lys Glu Leu Leu Gly Tyr Ile Arg Ala 435 440 445 Val Asn Phe Asn Gly Ser Ala Gly Thr Pro Val Thr Phe Asn Glu Asn 450 455 460 Gly Asp Ala Pro Gly Arg Tyr Asp Ile Phe Gln Tyr Gln Ile Thr Asn 465 470 475 480 Lys Ser Thr Glu Tyr Lys Val Ile Gly His Trp Thr Asn Gln Leu His 485 490 495 Leu Lys Val Glu Asp Met Gln Trp Ala His Arg Glu His Thr His Pro 500 505 510 Ala Ser Val Cys Ser Leu Pro Cys Lys Pro Gly Glu Arg Lys Lys Thr 515 520 525 Val Lys Gly Val Pro Cys Cys Trp His Cys Glu Arg Cys Glu Gly Tyr 530 535 540 Asn Tyr Gln Val Asp Glu Leu Ser Cys Glu Leu Cys Pro Leu Asp Gln 545 550 555 560 Arg Pro Asn Met Asn Arg Thr Gly Cys Gln Leu Ile Pro Ile Ile Lys 565 570 575 Leu Glu Trp His Ser Pro Trp Ala Val Val Pro Val Phe Val Ala Ile 580 585 590 Leu Gly Ile Ile Ala Thr Thr Phe Val Ile Val Thr Phe Val Arg Tyr 595 600 605 Asn Asp Thr Pro Ile Val Arg Ala Ser Gly Arg Glu Leu Ser Tyr Val 610 615 620 Leu Leu Thr Gly Ile Phe Leu Cys Tyr Ser Ile Thr Phe Leu Met Ile 625 630 635 640 Ala Ala Pro Asp Thr Ile Ile Cys Ser Phe Arg Arg Val Phe Leu Gly 645 650 655 Leu Gly Met Cys Phe Ser Tyr Ala Ala Leu Leu Thr Lys Thr Asn Arg 660 665 670 Ile His Arg Ile Phe Glu Gln Gly Lys Lys Ser Val Thr Ala Pro Lys 675 680 685 Phe Ile Ser Pro Ala Ser Gln Leu Val Ile Thr Phe Ser Leu Ile Ser 690 695 700 Val Gln Leu Leu Gly Val Phe Val Trp Phe Val Val Asp Pro Pro His 705 710 715 720 Ile Ile Ile Asp Tyr Gly Glu Gln Arg Thr Leu Asp Pro Glu Lys Ala 725 730 735 Arg Gly Val Leu Lys Cys Asp Ile Ser Asp Leu Ser Leu Ile Cys Ser 740 745 750 Leu Gly Tyr Ser Ile Leu Leu Met Val Thr Cys Thr Val Tyr Ala Asn 755 760 765 Lys Thr Arg Gly Val Pro Glu Thr Phe Asn Glu Ala Lys Pro Ile Gly 770 775 780 Phe Thr Met Tyr Thr Thr Cys Ile Ile Trp Leu Ala Phe Ile Pro Ile 785 790 795 800 Phe Phe Gly Thr Ala Gln Ser Ala Glu Lys Met Tyr Ile Gln Thr Thr 805 810 815 Thr Leu Thr Val Ser Met Ser Leu Ser Ala Ser Val Ser Leu Gly Met 820 825 830 Leu Tyr Met Pro Lys Val Tyr Ile Ile Ile Phe His Pro Glu Gln Asn 835 840 845 Val Gln Lys Arg Lys Arg Ser Phe Lys Ala Val Val Thr Ala Ala Thr 850 855 860 Met Gln Ser Lys Leu Ile Gln Lys Gly Asn Asp Arg Pro Asn Gly Glu 865 870 875 880 Val Lys Ser Glu Leu Cys Glu Ser Leu Glu Thr Asn Thr Ser Ser Thr 885 890 895 Lys Thr Thr Tyr Ile Ser Tyr Ser Asn His Ser Ile 900 905 87 2896 DNA Homo Sapiens 87 ctgatctgat cttatcttct ctcttctttt ctttgagtgt gaattttcct gtttccccca 60 ggctggagtg cagtggcgcg atgtcggctc actgcaacct ctgtctcccg ggttcaagcg 120 attctcctgc ctcagcctcc tgagtagctg ggactacagg cgcatgccac catgcccagc 180 taatttttgt atttttagta gagacagggt tttgccttgt tggccaggct ggtcttgaac 240 tcctgacctc aggcgatcca cccgcctcgg cccctgcaca gtgcctggca catagcaagt 300 gctcaataaa tatttggtaa gacaagaaca cataagcgac attcaaatga atgtcaattc 360 ctccctccca tggggtgagg gttaggagtc agctggattt ctacgataac ctccattatg 420 ctgtcttgct ccctccagat gacgtcagtt gccaaggtgt attacagtca gaccactcag 480 acagaaagcc ggcccctaat gggcccaggg atacgacggc ggagagtcct gacaaaagat 540 ggtcgcagca acgtgagaat ggagcacatt gccgacaagc gcttcctcta cctcaaggac 600 ctgtggacaa ccttcattga catgcagtgg cgctacaagc ttctgctctt ctctgcgacc 660 tttgcaggca catggttcct ctttggcgtg gtgtggtatc tggtagctgt ggcacatggg 720 gacctgctgg agctggaccc cccggccaac cacaccccct gtgtggtaca ggtgcacaca 780 ctcactggag ccttcctctt ctcccttgaa tcccaaacca ccattggcta tggcttccgc 840 tacatcagtg aggaatgtcc actggccatt gtgcttctta ttgcccagct ggtgctcacc 900 accatcctgg aaatcttcat cacaggtacc ttcctggcga agattgcccg gcccaagaag 960 cgggctgaga ccattcgttt cagccagcat gcagttgtgg cctcccacaa tggcaagccc 1020 tgcctcatga tccgagttgc caatatgcgc aaaagcctcc tcattggctg ccaggtgaca 1080 ggaaaactgc ttcagaccca ccaaaccaag gaaggggaga acatccggct caaccaggtc 1140 aatgtgactt tccaagtaga cacagcctct gacagcccct tccttattct accccttacc 1200 ttctatcatg tggtagatga gaccagtccc ttgaaagatc tccctcttcg cagtggtgag 1260 ggtgactttg agctggtgct gatcctaagt gggacagtgg agtccaccag tgccacctgt 1320 caggtgcgca cttcctacct gccagaggag atcctttggg gctacgagtt cacacctgcc 1380 atctcactgt cagccagtgg taaatacata gctgacttta gcctttttga ccaagttgtg 1440 aaagtggcct ctcctagtgg cctccgtgac agcactgtac gctacggaga ccctgaaaag 1500 ctcaagttgg aggagtcatt aagggagcaa gctgagaagg agggcagtgc ccttagtgtg 1560 cgcatcagca atgtctgatg acctgttccc actcccccat tcctctggtc tcttttcctc 1620 tcttccaatg ccctggtaag gaatactacc cgggtttact ggagatcccc cgaagcaccc 1680 atcctccact ccctcttctt taacccagtg gcctgttggt agcttaggcc aactggagtc 1740 caggttcgcc tcccactgtc ccctttccac ttccccagct tctgccccaa tacacatacc 1800 tcccttaagc caggatgggg gaaagagtgg gattaggctg aagtggctta gaaggcctca 1860 gccatgcttg gatactcaca ttaggaggac catgtggttg gaaggataga ctgcccccta 1920 cctcccacca ccaccatgaa gtttggtgac ttgaggctgg agctccctct gttacctttc 1980 catctagcaa gttcccaaag gcaagactct ctctgatggt cactttgtgg tctgtgcttt 2040 cagaaataca ggaatctgat atcaacatat cctagggttt ctaccaatct ctgttgaaag 2100 aagccagggt ttgccactgt gaagcttgat ttctgctggt gacttctgac cataagctag 2160 aaccatggtc gccactgttt tccctctgta gtttctcaag tgaacactct caggataccc 2220 agttccctca tagcctctgt tctcagagaa ttggagttgg cccaagaaac ataaacatat 2280 aaccacccat atctatcctg gattctgaac tcttcaattt ggagtgacta acacaagttg 2340 ttatctaaac ctttaaacct atcttccagg cagcccagag aagatctgtt tccctgtgtc 2400 ctgtgaatgg aaggacccaa gccaatatgt tcctttgaaa agagtccagt acccaggccc 2460 catggaaagg tctgaaaata atattccaga ttacactgta cctggcttct cttcttcctt 2520 tcctgctcag cctagatcct tcttccttaa ccccaactct ttgggagaag ggagggaaaa 2580 tgcaagggcc ttcctctctt aacacggatg ctcaagtaaa actagattca cagggcacag 2640 attccccaga aagttaacac aatcccacca tgagggatgg gtaaattctc agatttccaa 2700 actgctgtac agagcctctg agaattggtg atgctttgtt aaggtttggg caggagcaga 2760 actctgtggc tggcagccac tattctcagt tacacctccc agtgcccttc tgaaaagtgc 2820 cagctatttc attaggcaat gctggaagga aatgaaatta taccttctga tcaaataacc 2880 atggcttccc tcagcc 2896 88 379 PRT Homo Sapiens 88 Met Thr Ser Val Ala Lys Val Tyr Tyr Ser Gln Thr Thr Gln Thr Glu 1 5 10 15 Ser Arg Pro Leu Met Gly Pro Gly Ile Arg Arg Arg Arg Val Leu Thr 20 25 30 Lys Asp Gly Arg Ser Asn Val Arg Met Glu His Ile Ala Asp Lys Arg 35 40 45 Phe Leu Tyr Leu Lys Asp Leu Trp Thr Thr Phe Ile Asp Met Gln Trp 50 55 60 Arg Tyr Lys Leu Leu Leu Phe Ser Ala Thr Phe Ala Gly Thr Trp Phe 65 70 75 80 Leu Phe Gly Val Val Trp Tyr Leu Val Ala Val Ala His Gly Asp Leu 85 90 95 Leu Glu Leu Asp Pro Pro Ala Asn His Thr Pro Cys Val Val Gln Val 100 105 110 His Thr Leu Thr Gly Ala Phe Leu Phe Ser Leu Glu Ser Gln Thr Thr 115 120 125 Ile Gly Tyr Gly Phe Arg Tyr Ile Ser Glu Glu Cys Pro Leu Ala Ile 130 135 140 Val Leu Leu Ile Ala Gln Leu Val Leu Thr Thr Ile Leu Glu Ile Phe 145 150 155 160 Ile Thr Gly Thr Phe Leu Ala Lys Ile Ala Arg Pro Lys Lys Arg Ala 165 170 175 Glu Thr Ile Arg Phe Ser Gln His Ala Val Val Ala Ser His Asn Gly 180 185 190 Lys Pro Cys Leu Met Ile Arg Val Ala Asn Met Arg Lys Ser Leu Leu 195 200 205 Ile Gly Cys Gln Val Thr Gly Lys Leu Leu Gln Thr His Gln Thr Lys 210 215 220 Glu Gly Glu Asn Ile Arg Leu Asn Gln Val Asn Val Thr Phe Gln Val 225 230 235 240 Asp Thr Ala Ser Asp Ser Pro Phe Leu Ile Leu Pro Leu Thr Phe Tyr 245 250 255 His Val Val Asp Glu Thr Ser Pro Leu Lys Asp Leu Pro Leu Arg Ser 260 265 270 Gly Glu Gly Asp Phe Glu Leu Val Leu Ile Leu Ser Gly Thr Val Glu 275 280 285 Ser Thr Ser Ala Thr Cys Gln Val Arg Thr Ser Tyr Leu Pro Glu Glu 290 295 300 Ile Leu Trp Gly Tyr Glu Phe Thr Pro Ala Ile Ser Leu Ser Ala Ser 305 310 315 320 Gly Lys Tyr Ile Ala Asp Phe Ser Leu Phe Asp Gln Val Val Lys Val 325 330 335 Ala Ser Pro Ser Gly Leu Arg Asp Ser Thr Val Arg Tyr Gly Asp Pro 340 345 350 Glu Lys Leu Lys Leu Glu Glu Ser Leu Arg Glu Gln Ala Glu Lys Glu 355 360 365 Gly Ser Ala Leu Ser Val Arg Ile Ser Asn Val 370 375 89 1856 DNA Homo Sapiens 89 attgcgggcg gcggcgttcg gagtcgccgg gagctgccag gctgtccgcg ccgccgctgc 60 ggggccatga tccggaacgg gcgcggggct gcaggcggcg cagagcagcc gggcccgggg 120 ggcaggcgcg ccgtgagggt gtggtgcgat ggctgctatg acatggtgca ttacggccac 180 tccaaccagc tgcgccaggc acgggccatg ggtgactacc tcatcgtagg cgtgcacacc 240 gatgaggaga tcgccaagca caaggggccc ccggtgttca ctcaggagga gagatacaag 300 atggtgcagg ccatcaaatg ggtggacgag gtggtgccag cggctcccta cgtcactaca 360 ctagagaccc tggacaaata caactgtgac ttctgtgttc acggcaatga catcaccctg 420 actgtagatg gccgggacac ctatgaggaa gtaaagcagg ctgggaggta cagagaatgc 480 aagcgcacgc aaggggtgtc caccacagac ctcgtgggcc gcatgctgct ggtaaccaaa 540 gcccatcaca gcagccagga gatgtcctct gagtaccggg agtatgcaga cagttttggc 600 aagtgccctg gtgggcggaa cccctggacc ggggtatccc agttcctgca gacatctcag 660 aagatcatcc agtttgcttc tgggaaggag ccccagccag gggagacagt catctatgtg 720 gctggtgcct tcgacctgtt ccacatcggg catgtggact tcctggagaa ggtgcacagg 780 ctggcagaga ggccctacat catcgcgggc ttacactttg accaggaggt caatcactac 840 aaggggaaga actaccccat catgaatctg catgaacgga ctctgagcgt gctggcctgc 900 cggtacgtgt cagaagtggt gattggagcc ccgtacgcgg tcacagcaga gctcctaagt 960 cacttcaagg tggacctggt gtgtcacggc aagacagaaa ttatccctga cagggatggc 1020 tccgacccat accaggagcc caagagaagg ggcatcttcc gtcagattga cagtggcagc 1080 aacctcacca cagacctcat cgtccagcgg atcatcacca acaggttgga gtatgaggcg 1140 cgaaaccaga agaaggaagc caaggagctg gccttcctgg aggctgccag gcagcaggcg 1200 gcacagcccc tgggggagcg cgatggtgac ttctaacctg gcagaggccc tggccggccc 1260 tccccctgct ctgcttctgc gccttctgcg tttggacata ggactctgca gggccgccct 1320 ctctaactgg cctggctctg gaagggctgg tgaggactct gcctccttgc ctgcctacaa 1380 ggtgcctggt ttgcagcagg ctctccgctc tttccagcaa agctgctcag agagggtgtc 1440 cagcacagtg gagaggccgg aagtgagacg ggcagacggc acctgcagcc tgaaacgcac 1500 cgctcctgcg tgcgccccca cctggtcccc ggatgccccc accacctgga cagaggccac 1560 actgactgcc cacccagctg tggcgggagg tgcagagcag ggggctttag ggagcagtga 1620 ctgcggtcac ccctttagtt ctctgggtgt agaccacacc acctcccact gggcaccccc 1680 caacacggtg tcctgccacc cagcgcctgg ctccaggaaa acacgcttgc cttccttccc 1740 ggcagcttcg ccactctcct tatggactct gttctgtttg tacatggctg acggaaatct 1800 ctttggtaca accgaataaa gcctggtggc agtgctgcgc ggggctccca gccaat 1856 90 389 PRT Homo Sapiens 90 Met Ile Arg Asn Gly Arg Gly Ala Ala Gly Gly Ala Glu Gln Pro Gly 1 5 10 15 Pro Gly Gly Arg Arg Ala Val Arg Val Trp Cys Asp Gly Cys Tyr Asp 20 25 30 Met Val His Tyr Gly His Ser Asn Gln Leu Arg Gln Ala Arg Ala Met 35 40 45 Gly Asp Tyr Leu Ile Val Gly Val His Thr Asp Glu Glu Ile Ala Lys 50 55 60 His Lys Gly Pro Pro Val Phe Thr Gln Glu Glu Arg Tyr Lys Met Val 65 70 75 80 Gln Ala Ile Lys Trp Val Asp Glu Val Val Pro Ala Ala Pro Tyr Val 85 90 95 Thr Thr Leu Glu Thr Leu Asp Lys Tyr Asn Cys Asp Phe Cys Val His 100 105 110 Gly Asn Asp Ile Thr Leu Thr Val Asp Gly Arg Asp Thr Tyr Glu Glu 115 120 125 Val Lys Gln Ala Gly Arg Tyr Arg Glu Cys Lys Arg Thr Gln Gly Val 130 135 140 Ser Thr Thr Asp Leu Val Gly Arg Met Leu Leu Val Thr Lys Ala His 145 150 155 160 His Ser Ser Gln Glu Met Ser Ser Glu Tyr Arg Glu Tyr Ala Asp Ser 165 170 175 Phe Gly Lys Cys Pro Gly Gly Arg Asn Pro Trp Thr Gly Val Ser Gln 180 185 190 Phe Leu Gln Thr Ser Gln Lys Ile Ile Gln Phe Ala Ser Gly Lys Glu 195 200 205 Pro Gln Pro Gly Glu Thr Val Ile Tyr Val Ala Gly Ala Phe Asp Leu 210 215 220 Phe His Ile Gly His Val Asp Phe Leu Glu Lys Val His Arg Leu Ala 225 230 235 240 Glu Arg Pro Tyr Ile Ile Ala Gly Leu His Phe Asp Gln Glu Val Asn 245 250 255 His Tyr Lys Gly Lys Asn Tyr Pro Ile Met Asn Leu His Glu Arg Thr 260 265 270 Leu Ser Val Leu Ala Cys Arg Tyr Val Ser Glu Val Val Ile Gly Ala 275 280 285 Pro Tyr Ala Val Thr Ala Glu Leu Leu Ser His Phe Lys Val Asp Leu 290 295 300 Val Cys His Gly Lys Thr Glu Ile Ile Pro Asp Arg Asp Gly Ser Asp 305 310 315 320 Pro Tyr Gln Glu Pro Lys Arg Arg Gly Ile Phe Arg Gln Ile Asp Ser 325 330 335 Gly Ser Asn Leu Thr Thr Asp Leu Ile Val Gln Arg Ile Ile Thr Asn 340 345 350 Arg Leu Glu Tyr Glu Ala Arg Asn Gln Lys Lys Glu Ala Lys Glu Leu 355 360 365 Ala Phe Leu Glu Ala Ala Arg Gln Gln Ala Ala Gln Pro Leu Gly Glu 370 375 380 Arg Asp Gly Asp Phe 385 91 3165 DNA Homo Sapiens 91 gtggctgcgc cgggctgcga cactgcagtt gtctacgcgg ccggggccgg gacgaggagg 60 cgttggacgg ggtcgcatac gttcgtcccc tcgcattgcg gccccgacag ctgcgccagg 120 atccccgggc ggcggcgcgg ggcgtgaacg ctctggggct cagccaggcc tgcgcgggcc 180 cgaggccgga ggaacccgga ctccggcgta gcggttttga cacaagggcg catatcttca 240 aagcacctag tacctcctac cattgtcaac tgatacagaa ttcgttgttg ggaaggactg 300 gggaaacagc tgtaacattt gccaccctca gaagctgctg gtcctgtgtc acaccacctt 360 agcctcttga tcgaggaaga ttctcgctga agtctgttaa ttctactttt tgagtactta 420 tgaataacca cgtgtcttca aaaccatcta ccatgaagct aaaacatacc atcaacccta 480 ttcttttata ttttatacat tttctaatat cactttatac tattttaaca tacattccgt 540 tttatttttt ctccgagtca agacaagaaa aatcaaaccg aattaaagca aagcctgtaa 600 attcaaaacc tgattctgca tacagatctg ttaatagttt ggatggtttg gcttcagtat 660 tataccctgg atgtgatact ttagataaag tttttacata tgcaaaaaac aaatttaaga 720 acaaaagact cttgggaaca cgtgaagttt taaatgagga agatgaagta caaccaaatg 780 gaaaaatttt taaaaaggtt attcttggac agtataattg gctttcctat gaagatgtct 840 ttgttcgagc ctttaatttt ggaaatggat tacagatgtt gggtcagaaa ccaaagacca 900 acatcgccat cttctgtgag accagggccg agtggatgat agctgcacag gcgtgtttta 960 tgtataattt tcagcttgtt acattatatg ccactctagg aggtccagcc attgttcatg 1020 cattaaatga aacagaggtg accaacatca ttactagtaa agaactctta caaacaaagt 1080 tgaaggatat agtttctttg gtcccacgcc tgcggcacat catcactgtt gatggaaagc 1140 caccgacctg gtccgacttc cccaagggca tcattgtgca taccatggct gcagtggagg 1200 ccctgggagc caaggccagc atggaaaacc aacctcatag caaaccattg ccctcagata 1260 ttgcagtaat catgtacaca agtggatcca caggacttcc aaagggagtc atgatctcac 1320 atagtaacat tattgctggt ataactggga tggcagaaag gattccagaa ctaggagagg 1380 aagatgtcta cattggatat ttgcctctgg cccatgttct agaattaagt gctgagcttg 1440 tctgtctttc tcacggatgc cgcattggtt actcttcacc acagacttta gcagatcagt 1500 cttcaaaaat taaaaaagga agcaaagggg atacatccat gttgaaacca acactgatgg 1560 cagcagttcc ggaaatcatg gatcggatct acaaaaatgt catgaataaa gtcagtgaaa 1620 tgagtagttt tcaacgtaat ctgtttattc tggcctataa ttacaaaatg gaacagattt 1680 caaaaggacg taatactcca ctgtgcgaca gctttgtttt ccggaaagtt cgaagcttgc 1740 tagggggaaa tattcgtctc ctgttgtgtg gtggcgctcc actttctgca accacgcagc 1800 gattcatgaa catctgtttc tgctgtcctg ttggtcaggg atacgggctc actgaatctg 1860 ctggggctgg aacaatttcc gaagtgtggg actacaatac tggcagagtg ggagcaccat 1920 tagtttgctg tgaaatcaaa ttaaaaaact gggaggaagg tggatacttt aatactgata 1980 agccacaccc caggggtgaa attcttattg ggggccaaag tgtgacaatg gggtactaca 2040 aaaatgaagc aaaaacaaaa gctgatttct ctgaagatga aaatggacaa aggtggctct 2100 gtactgggga tattggagag tttgaacccg atggatgctt aaagattatt gatcgtaaaa 2160 aggaccttgt aaaactacag gcaggggaat atgtttctct tgggaaagta gaggcagctt 2220 tgaagaatct tccactagta gataacattt gtgcatatgc aaacagttat cattcttatg 2280 tcattggatt tgttgtgcca aatcaaaagg aactaactga actagctcga aagaaaggac 2340 ttaaagggac ttgggaggag ctgtgtaaca gttgtgaaat ggaaaatgag gtacttaaag 2400 tgctttccga agctgctatt tcagcaagtc tggaaaagtt tgaaattcca gtaaaaattc 2460 gtttgagtcc tgaaccgtgg acccctgaaa ctggtctggt gacagatgcc ttcaagctga 2520 aacgcaaaga gcttaaaaca cattaccagg cggacattga gcgaatgtat ggaagaaaat 2580 aattattctc ttctggcatc agtttgctac agtgagctca catcaaatag gaaaatactt 2640 gaaatgcatg tctcaagctg caaggcaaac tccattcctc atattaaact attacttctc 2700 atgacgtcac catttttaac tgacaggatt agtaaaacat taagacagca aacttgtgtc 2760 tgtctcttct ttcattttcc ccgccaccaa cttactttac cacctatgac tgtacttgtc 2820 agtatgagaa tttttctgaa tcatattggg gaagcagtga ttttaaaacc tcaagttttt 2880 aaacatgatt tatatgttct gtataatgtt cagtttgtaa ctttttaaaa gtttggatgt 2940 atagagggat aaataggaaa tataagaatt ggttatttgg gggctttttt acttactgta 3000 tttaaaaata caagggtatt gatatgaaat tatgtaaatt tcaaatgctt atgaatcaaa 3060 tcattgttga acaaaagatt tgttgctgtg taattattgt cttgtatgca tttgagagaa 3120 ataaatatac ccatacttat gttttaagaa gttgagatct tgtga 3165 92 720 PRT Homo Sapiens 92 Met Asn Asn His Val Ser Ser Lys Pro Ser Thr Met Lys Leu Lys His 1 5 10 15 Thr Ile Asn Pro Ile Leu Leu Tyr Phe Ile His Phe Leu Ile Ser Leu 20 25 30 Tyr Thr Ile Leu Thr Tyr Ile Pro Phe Tyr Phe Phe Ser Glu Ser Arg 35 40 45 Gln Glu Lys Ser Asn Arg Ile Lys Ala Lys Pro Val Asn Ser Lys Pro 50 55 60 Asp Ser Ala Tyr Arg Ser Val Asn Ser Leu Asp Gly Leu Ala Ser Val 65 70 75 80 Leu Tyr Pro Gly Cys Asp Thr Leu Asp Lys Val Phe Thr Tyr Ala Lys 85 90 95 Asn Lys Phe Lys Asn Lys Arg Leu Leu Gly Thr Arg Glu Val Leu Asn 100 105 110 Glu Glu Asp Glu Val Gln Pro Asn Gly Lys Ile Phe Lys Lys Val Ile 115 120 125 Leu Gly Gln Tyr Asn Trp Leu Ser Tyr Glu Asp Val Phe Val Arg Ala 130 135 140 Phe Asn Phe Gly Asn Gly Leu Gln Met Leu Gly Gln Lys Pro Lys Thr 145 150 155 160 Asn Ile Ala Ile Phe Cys Glu Thr Arg Ala Glu Trp Met Ile Ala Ala 165 170 175 Gln Ala Cys Phe Met Tyr Asn Phe Gln Leu Val Thr Leu Tyr Ala Thr 180 185 190 Leu Gly Gly Pro Ala Ile Val His Ala Leu Asn Glu Thr Glu Val Thr 195 200 205 Asn Ile Ile Thr Ser Lys Glu Leu Leu Gln Thr Lys Leu Lys Asp Ile 210 215 220 Val Ser Leu Val Pro Arg Leu Arg His Ile Ile Thr Val Asp Gly Lys 225 230 235 240 Pro Pro Thr Trp Ser Asp Phe Pro Lys Gly Ile Ile Val His Thr Met 245 250 255 Ala Ala Val Glu Ala Leu Gly Ala Lys Ala Ser Met Glu Asn Gln Pro 260 265 270 His Ser Lys Pro Leu Pro Ser Asp Ile Ala Val Ile Met Tyr Thr Ser 275 280 285 Gly Ser Thr Gly Leu Pro Lys Gly Val Met Ile Ser His Ser Asn Ile 290 295 300 Ile Ala Gly Ile Thr Gly Met Ala Glu Arg Ile Pro Glu Leu Gly Glu 305 310 315 320 Glu Asp Val Tyr Ile Gly Tyr Leu Pro Leu Ala His Val Leu Glu Leu 325 330 335 Ser Ala Glu Leu Val Cys Leu Ser His Gly Cys Arg Ile Gly Tyr Ser 340 345 350 Ser Pro Gln Thr Leu Ala Asp Gln Ser Ser Lys Ile Lys Lys Gly Ser 355 360 365 Lys Gly Asp Thr Ser Met Leu Lys Pro Thr Leu Met Ala Ala Val Pro 370 375 380 Glu Ile Met Asp Arg Ile Tyr Lys Asn Val Met Asn Lys Val Ser Glu 385 390 395 400 Met Ser Ser Phe Gln Arg Asn Leu Phe Ile Leu Ala Tyr Asn Tyr Lys 405 410 415 Met Glu Gln Ile Ser Lys Gly Arg Asn Thr Pro Leu Cys Asp Ser Phe 420 425 430 Val Phe Arg Lys Val Arg Ser Leu Leu Gly Gly Asn Ile Arg Leu Leu 435 440 445 Leu Cys Gly Gly Ala Pro Leu Ser Ala Thr Thr Gln Arg Phe Met Asn 450 455 460 Ile Cys Phe Cys Cys Pro Val Gly Gln Gly Tyr Gly Leu Thr Glu Ser 465 470 475 480 Ala Gly Ala Gly Thr Ile Ser Glu Val Trp Asp Tyr Asn Thr Gly Arg 485 490 495 Val Gly Ala Pro Leu Val Cys Cys Glu Ile Lys Leu Lys Asn Trp Glu 500 505 510 Glu Gly Gly Tyr Phe Asn Thr Asp Lys Pro His Pro Arg Gly Glu Ile 515 520 525 Leu Ile Gly Gly Gln Ser Val Thr Met Gly Tyr Tyr Lys Asn Glu Ala 530 535 540 Lys Thr Lys Ala Asp Phe Ser Glu Asp Glu Asn Gly Gln Arg Trp Leu 545 550 555 560 Cys Thr Gly Asp Ile Gly Glu Phe Glu Pro Asp Gly Cys Leu Lys Ile 565 570 575 Ile Asp Arg Lys Lys Asp Leu Val Lys Leu Gln Ala Gly Glu Tyr Val 580 585 590 Ser Leu Gly Lys Val Glu Ala Ala Leu Lys Asn Leu Pro Leu Val Asp 595 600 605 Asn Ile Cys Ala Tyr Ala Asn Ser Tyr His Ser Tyr Val Ile Gly Phe 610 615 620 Val Val Pro Asn Gln Lys Glu Leu Thr Glu Leu Ala Arg Lys Lys Gly 625 630 635 640 Leu Lys Gly Thr Trp Glu Glu Leu Cys Asn Ser Cys Glu Met Glu Asn 645 650 655 Glu Val Leu Lys Val Leu Ser Glu Ala Ala Ile Ser Ala Ser Leu Glu 660 665 670 Lys Phe Glu Ile Pro Val Lys Ile Arg Leu Ser Pro Glu Pro Trp Thr 675 680 685 Pro Glu Thr Gly Leu Val Thr Asp Ala Phe Lys Leu Lys Arg Lys Glu 690 695 700 Leu Lys Thr His Tyr Gln Ala Asp Ile Glu Arg Met Tyr Gly Arg Lys 705 710 715 720 93 1124 DNA Homo Sapiens 93 atcaaaattt actctgcgag actctgctga actggctgca tcagggagaa atttcatctc 60 ccagaagggt gttgctcatc gtttcttccc ggaaacatct gcagagacta gcttttcagg 120 ctaaggtatc ctccatgatg ttaccattgc aaggtgccca gatgctgcag atgctggaga 180 aatccttgag gaagagcctc ccagcatcct taaaggttta tggaactgtc tttcacataa 240 accatggaaa tccattcaat ctgaaggctg tggtggacaa gtggcctgat tttaatacag 300 tggttgtctg ccctcaggag caggatatga cagatgacct tgatcactat accaatactt 360 accaaatcta ctccaaagat ccccaaaact gtcaggaatt ccttggatca ccagaactca 420 tcaactggaa acagcattta cagattcaaa gttcacagcc tagcctgaat gaggctatac 480 aaaatcttgc agccattaag tccttcaaag tcaaacaaac acaacgcatt ctctatatgg 540 cagctgaaac agccaaggaa ctgactcctt tcctgctgaa atcaaagatt ttatctccca 600 gtggtggcaa acccaaggcc atcaaccaag agatgtttaa actctcatcc atggatgtta 660 cccatgctca cttggtgaat aaattctggc attttggtgg taatgagagg agccagagat 720 tcattgagcg ctgcattcag acctttccca cctgctgtct cctggggcct gaggggaccc 780 ctgtgtgctg ggatctaatg gaccagactg gagagatgag aatggcaggc accttcgcgg 840 aataccggct ccatggcctt gtgacgtatg tcatctattc ccacgcccag aaattgggca 900 aacttgggtt tcctgtctat tctcatgtag actacagcaa tgaagctatg caaaaaatga 960 gttacacact gcaacatgtt cccattccca gaagctggaa ccagtggaac tgtgtacctc 1020 tgtgatgcca atcctgaaca taagacagtg ttgggcaggt ctgggcgtat aatttgagga 1080 gtggatggtg gatgggaaga attaattaag cggtcgcaag ctta 1124 94 296 PRT Homo Sapiens 94 Met Met Leu Pro Leu Gln Gly Ala Gln Met Leu Gln Met Leu Glu Lys 1 5 10 15 Ser Leu Arg Lys Ser Leu Pro Ala Ser Leu Lys Val Tyr Gly Thr Val 20 25 30 Phe His Ile Asn His Gly Asn Pro Phe Asn Leu Lys Ala Val Val Asp 35 40 45 Lys Trp Pro Asp Phe Asn Thr Val Val Val Cys Pro Gln Glu Gln Asp 50 55 60 Met Thr Asp Asp Leu Asp His Tyr Thr Asn Thr Tyr Gln Ile Tyr Ser 65 70 75 80 Lys Asp Pro Gln Asn Cys Gln Glu Phe Leu Gly Ser Pro Glu Leu Ile 85 90 95 Asn Trp Lys Gln His Leu Gln Ile Gln Ser Ser Gln Pro Ser Leu Asn 100 105 110 Glu Ala Ile Gln Asn Leu Ala Ala Ile Lys Ser Phe Lys Val Lys Gln 115 120 125 Thr Gln Arg Ile Leu Tyr Met Ala Ala Glu Thr Ala Lys Glu Leu Thr 130 135 140 Pro Phe Leu Leu Lys Ser Lys Ile Leu Ser Pro Ser Gly Gly Lys Pro 145 150 155 160 Lys Ala Ile Asn Gln Glu Met Phe Lys Leu Ser Ser Met Asp Val Thr 165 170 175 His Ala His Leu Val Asn Lys Phe Trp His Phe Gly Gly Asn Glu Arg 180 185 190 Ser Gln Arg Phe Ile Glu Arg Cys Ile Gln Thr Phe Pro Thr Cys Cys 195 200 205 Leu Leu Gly Pro Glu Gly Thr Pro Val Cys Trp Asp Leu Met Asp Gln 210 215 220 Thr Gly Glu Met Arg Met Ala Gly Thr Phe Ala Glu Tyr Arg Leu His 225 230 235 240 Gly Leu Val Thr Tyr Val Ile Tyr Ser His Ala Gln Lys Leu Gly Lys 245 250 255 Leu Gly Phe Pro Val Tyr Ser His Val Asp Tyr Ser Asn Glu Ala Met 260 265 270 Gln Lys Met Ser Tyr Thr Leu Gln His Val Pro Ile Pro Arg Ser Trp 275 280 285 Asn Gln Trp Asn Cys Val Pro Leu 290 295 95 3040 DNA Homo Sapiens misc_feature (1)...(3040) n = A,T,C or G 95 gacgggtctg caccaacctc agtttcgggg ctgcggctca cagaagtcta acctgcccgg 60 gacgcccgca ccaactcctg ccgcgcggtc cttccaaccc tcctgctacc atgaagattg 120 cagtgattgg acagagcctg tttggccagg aagtttactg ccacctgagg aaggagggcc 180 acgaagtggt gggtgtgttc actgttccag acaaggatgg aaaggccgac cccctgggtc 240 tggaagctga gaaggatgga gtgccggtat tcaagtactc ccggtggcgt gcaaaagcgc 300 aagctttgcc tgatgtggtg gcaaaatacc aggctttggg ggccgaactc aacgtcctgc 360 cctcctgcag ccaattcatc cccatggaga taatcagtgc cccccggcat ggctccatca 420 tctatcaccc gtcactgctc cctaggcacc gaggggcctc ggccatcaac tggaccctca 480 ttcacggaga taagaaaggg gggttttcca tcttctgggc ggatgatggt ctggacaccg 540 gagacctgct gctgcagaag gagtgtgagg tgctcccgga cgacaccgtg agcacgctgt 600 acaaccgctt cctcttccct gaaggcatca aaggggtggt gcaggccgtg aggctgatcg 660 ctgagggcaa agcccccaga ctccctcagc ctaaggaagg agccacctat gaggggattc 720 agaagaagga gacagccaag atcaactggg accagccggc agaggccatt cacaactgga 780 tccgcgggaa cgacaaggtg ccgggagcct ggacagaggc ctgtgaacag aaactgacat 840 ttttcaactc aacgctgaac acttcaggcc tggtgcccga gggagacgct ttgcccatcc 900 caggagccca tcggccaggg gtggtcacca aagcaggact catcctcttt gggaatgatg 960 acaaaatgct gctggtgaag aatattcagc tggaggatgg caaaatgatc ctggcctcga 1020 acttctttaa gggggcagcc agcagtgtcc ttgagctgac agaggcagag ctggttactg 1080 cggaggctgt gcggagtgtt tggcagcgga tcctccccaa agtactggag gttgaagact 1140 ccactgattt cttcaagtca ggggccgcgt ctgtggacgt tgtgaggctg gtggaggaag 1200 tgaaggagct gtgtgatggc ctggagttag aaaatgaaga tgtgtacatg gcatccacct 1260 ttggggactt catccagctg ttagtgagga agctgcgagg ggacgatgag gagggcgagt 1320 gcagcattga ctacgtggaa atggcagtga acaagcgcac tgtccgcatg ccccaccagc 1380 tcttcattgg gggggagttc gtggatgccg agggcgccaa gacctctgag accatcaatc 1440 ccaccgatgg aagtgtcatc tgccaggtat ccctggccca agtcaccgac gtcgacaagg 1500 cagtggccgc ngccaagggt gcctttgaga atggacggtg ggggaagatc agtgcgcggg 1560 accggggccg gctgatgtac aggttggcag atctcatgga gcagcaccag gaggagctgg 1620 ccaccattga ggccctggat gcgggtgccg tctacacgct ggccctgaag acccacgtgg 1680 gcatgtccat ccagaccttc cgatactttg ctggctggtg tgacaagatc cagggctcca 1740 ccatccccat caaccaggcc agacccaacc gcaacctgac cttgaccagg aaggagcctg 1800 ttggggtttg tggcatcatc atcccctgga actatcccct gatgatgctg tcctggaaga 1860 cagctgcctg cctggctgcc gggaacacag tggtgatcaa gcctgctcag gtgaccccac 1920 tcacagcctt gaagtttgca gagctgacat taaaggccgg gattcccaaa ggtgtggtca 1980 acgtcctccc aggatctggc tccctggtcg gccagagact ctcagaccat cctgatgtga 2040 ggaaaatcgg gttcacaggc tccacagagg tgggcaagca catcatgaaa agctgtgcca 2100 taagtaacgt gaagaaggtg tccctggaac tgggcgggga gtcacccttc atcatctttg 2160 ctgactgtga cctcaacaag gctgtgcaga tggggatgag ttctgttttc ttcagcaaag 2220 gagagaattg cattgcagca ggccgactct ttgtggagga ctccattcat gatgagttcg 2280 tgcggagagt ggtagaagag gtgcggaaga tgaaggtggg caacccgctg gacagggaca 2340 ccgaccacgg gccgcagaat caccatgccc accttgtgaa gctgatggag tactgccagc 2400 atggcgtgaa ggaaggggcc acactggtct gcggcgggaa tcaggtccct cggccagggt 2460 tcttctttga gccaactgtt ttcacagacg tggaagacca catgttcata gccaaggagg 2520 agtccttcgg gcctgtcatg atcatctctc ggtttgctga tggggacttg gatgccgtgc 2580 tgtctcgggc caatgccacg gaatttggcc tggcttctgg tgtcttcacc agggacatca 2640 acaaggccct gtatgtcagt gacaagctcc aggcaggcac tgtgtttgtc aacacgtaca 2700 acaagaccga cgtggccgct cccttcggag gattcaaaca gtctggattt ggcaaagatc 2760 taggagaggc ggctctgaac gagtacctgc gggtcaagac agtgaccttc gaatactgaa 2820 gaaaggtctg tgtgagaaga aagtccctgc ccctccctcg tggntggggc cccctccctc 2880 ttgagcctgg gtgcacagca cctcccacct ggggggctag tggaagccct cctgcctgca 2940 caccatgtnt gcatcttgga cgccctctgt ccagtcagaa gcagcccttg gctgggtgag 3000 gtgtgcccct cccagggaga ataaagcttc tgaagataaa 3040 96 902 PRT Homo Sapiens 96 Met Lys Ile Ala Val Ile Gly Gln Ser Leu Phe Gly Gln Glu Val Tyr 1 5 10 15 Cys His Leu Arg Lys Glu Gly His Glu Val Val Gly Val Phe Thr Val 20 25 30 Pro Asp Lys Asp Gly Lys Ala Asp Pro Leu Gly Leu Glu Ala Glu Lys 35 40 45 Asp Gly Val Pro Val Phe Lys Tyr Ser Arg Trp Arg Ala Lys Ala Gln 50 55 60 Ala Leu Pro Asp Val Val Ala Lys Tyr Gln Ala Leu Gly Ala Glu Leu 65 70 75 80 Asn Val Leu Pro Ser Cys Ser Gln Phe Ile Pro Met Glu Ile Ile Ser 85 90 95 Ala Pro Arg His Gly Ser Ile Ile Tyr His Pro Ser Leu Leu Pro Arg 100 105 110 His Arg Gly Ala Ser Ala Ile Asn Trp Thr Leu Ile His Gly Asp Lys 115 120 125 Lys Gly Gly Phe Ser Ile Phe Trp Ala Asp Asp Gly Leu Asp Thr Gly 130 135 140 Asp Leu Leu Leu Gln Lys Glu Cys Glu Val Leu Pro Asp Asp Thr Val 145 150 155 160 Ser Thr Leu Tyr Asn Arg Phe Leu Phe Pro Glu Gly Ile Lys Gly Val 165 170 175 Val Gln Ala Val Arg Leu Ile Ala Glu Gly Lys Ala Pro Arg Leu Pro 180 185 190 Gln Pro Lys Glu Gly Ala Thr Tyr Glu Gly Ile Gln Lys Lys Glu Thr 195 200 205 Ala Lys Ile Asn Trp Asp Gln Pro Ala Glu Ala Ile His Asn Trp Ile 210 215 220 Arg Gly Asn Asp Lys Val Pro Gly Ala Trp Thr Glu Ala Cys Glu Gln 225 230 235 240 Lys Leu Thr Phe Phe Asn Ser Thr Leu Asn Thr Ser Gly Leu Val Pro 245 250 255 Glu Gly Asp Ala Leu Pro Ile Pro Gly Ala His Arg Pro Gly Val Val 260 265 270 Thr Lys Ala Gly Leu Ile Leu Phe Gly Asn Asp Asp Lys Met Leu Leu 275 280 285 Val Lys Asn Ile Gln Leu Glu Asp Gly Lys Met Ile Leu Ala Ser Asn 290 295 300 Phe Phe Lys Gly Ala Ala Ser Ser Val Leu Glu Leu Thr Glu Ala Glu 305 310 315 320 Leu Val Thr Ala Glu Ala Val Arg Ser Val Trp Gln Arg Ile Leu Pro 325 330 335 Lys Val Leu Glu Val Glu Asp Ser Thr Asp Phe Phe Lys Ser Gly Ala 340 345 350 Ala Ser Val Asp Val Val Arg Leu Val Glu Glu Val Lys Glu Leu Cys 355 360 365 Asp Gly Leu Glu Leu Glu Asn Glu Asp Val Tyr Met Ala Ser Thr Phe 370 375 380 Gly Asp Phe Ile Gln Leu Leu Val Arg Lys Leu Arg Gly Asp Asp Glu 385 390 395 400 Glu Gly Glu Cys Ser Ile Asp Tyr Val Glu Met Ala Val Asn Lys Arg 405 410 415 Thr Val Arg Met Pro His Gln Leu Phe Ile Gly Gly Glu Phe Val Asp 420 425 430 Ala Glu Gly Ala Lys Thr Ser Glu Thr Ile Asn Pro Thr Asp Gly Ser 435 440 445 Val Ile Cys Gln Val Ser Leu Ala Gln Val Thr Asp Val Asp Lys Ala 450 455 460 Val Ala Ala Ala Lys Gly Ala Phe Glu Asn Gly Arg Trp Gly Lys Ile 465 470 475 480 Ser Ala Arg Asp Arg Gly Arg Leu Met Tyr Arg Leu Ala Asp Leu Met 485 490 495 Glu Gln His Gln Glu Glu Leu Ala Thr Ile Glu Ala Leu Asp Ala Gly 500 505 510 Ala Val Tyr Thr Leu Ala Leu Lys Thr His Val Gly Met Ser Ile Gln 515 520 525 Thr Phe Arg Tyr Phe Ala Gly Trp Cys Asp Lys Ile Gln Gly Ser Thr 530 535 540 Ile Pro Ile Asn Gln Ala Arg Pro Asn Arg Asn Leu Thr Leu Thr Arg 545 550 555 560 Lys Glu Pro Val Gly Val Cys Gly Ile Ile Ile Pro Trp Asn Tyr Pro 565 570 575 Leu Met Met Leu Ser Trp Lys Thr Ala Ala Cys Leu Ala Ala Gly Asn 580 585 590 Thr Val Val Ile Lys Pro Ala Gln Val Thr Pro Leu Thr Ala Leu Lys 595 600 605 Phe Ala Glu Leu Thr Leu Lys Ala Gly Ile Pro Lys Gly Val Val Asn 610 615 620 Val Leu Pro Gly Ser Gly Ser Leu Val Gly Gln Arg Leu Ser Asp His 625 630 635 640 Pro Asp Val Arg Lys Ile Gly Phe Thr Gly Ser Thr Glu Val Gly Lys 645 650 655 His Ile Met Lys Ser Cys Ala Ile Ser Asn Val Lys Lys Val Ser Leu 660 665 670 Glu Leu Gly Gly Glu Ser Pro Phe Ile Ile Phe Ala Asp Cys Asp Leu 675 680 685 Asn Lys Ala Val Gln Met Gly Met Ser Ser Val Phe Phe Ser Lys Gly 690 695 700 Glu Asn Cys Ile Ala Ala Gly Arg Leu Phe Val Glu Asp Ser Ile His 705 710 715 720 Asp Glu Phe Val Arg Arg Val Val Glu Glu Val Arg Lys Met Lys Val 725 730 735 Gly Asn Pro Leu Asp Arg Asp Thr Asp His Gly Pro Gln Asn His His 740 745 750 Ala His Leu Val Lys Leu Met Glu Tyr Cys Gln His Gly Val Lys Glu 755 760 765 Gly Ala Thr Leu Val Cys Gly Gly Asn Gln Val Pro Arg Pro Gly Phe 770 775 780 Phe Phe Glu Pro Thr Val Phe Thr Asp Val Glu Asp His Met Phe Ile 785 790 795 800 Ala Lys Glu Glu Ser Phe Gly Pro Val Met Ile Ile Ser Arg Phe Ala 805 810 815 Asp Gly Asp Leu Asp Ala Val Leu Ser Arg Ala Asn Ala Thr Glu Phe 820 825 830 Gly Leu Ala Ser Gly Val Phe Thr Arg Asp Ile Asn Lys Ala Leu Tyr 835 840 845 Val Ser Asp Lys Leu Gln Ala Gly Thr Val Phe Val Asn Thr Tyr Asn 850 855 860 Lys Thr Asp Val Ala Ala Pro Phe Gly Gly Phe Lys Gln Ser Gly Phe 865 870 875 880 Gly Lys Asp Leu Gly Glu Ala Ala Leu Asn Glu Tyr Leu Arg Val Lys 885 890 895 Thr Val Thr Phe Glu Tyr 900 97 3095 DNA Homo Sapiens 97 gggtcgaccc acgcgtccgg agccagcgag gagtgaagct gagcctggcc tcacacgctc 60 ctagaggacc acctcctgag agagttcttt caccccctct tctttctcca agctcccctc 120 ctgctctccc tccctgccca atacaatgca ttcttgagtg gcagcgtctg gactccaggc 180 agccccagag aaccgaagca agccaaagag aggactggag ccaagatact ggtgggggag 240 attggatgcc tggctttctt tgaggacatc tttggagcga gggtggcttt ggggtggggg 300 cttgtgctgc agggaataca gccaggcccc aagatggaca cttctgggca cttccatgac 360 tcgggggtgg gggacttgga tgaagacccc aagtgcccct gtccatcctc tggggatgag 420 cagcagcagc agcagcagca gcaacagcag cagcagccac caccgccagc gccaccagca 480 gccccccagc agcccctggg accctcgctg cagcctcagc ctccgcagct tcagcagcag 540 cagcagcagc agcagcagca gcagcagcag cagcagcagc agcagcagcc accgcatccc 600 ctgtctcagc tcgcccaact ccagagccag cccgtccacc ctggcctgct gcactcctct 660 cccaccgctt tcagggcccc cccttcgtcc aactccaccg ccatcctcca cccttcctcc 720 aggcaaggca gccagctcaa tctcaatgac cacttgcttg gccactctcc aagttccaca 780 gctacaagtg ggcctggcgg aggcagccgg caccgacagg ccagccccct ggtgcaccgg 840 cgggacagca accccttcac ggagatcgcc atgagctcct gcaagtatag cggtggggtc 900 atgaagcccc tcagccgcct cagcgcctcc cggaggaacc tcatcgaggc cgagactgag 960 ggccaacccc tccagctttt cagccctagc aaccccccgg agatcgtcat ctcctcccgg 1020 gaggacaacc atgcccacca gaccctgctc catcacccta atgccaccca caaccaccag 1080 catgccggca ccaccgccag cagcaccacc ttccccaaag ccaacaagcg gaaaaaccaa 1140 aacattggct ataagctggg acacaggagg gccctgtttg aaaagagaaa gcgactgagt 1200 gactatgctc tgatttttgg gatgtttgga attgttgtta tggtgataga gaccgagctc 1260 tcttggggtt tgtactcaaa ggactccatg ttttcgttgg ccctgaaatg ccttatcagt 1320 ctgtccacca tcatcctttt gggcttgatc atcgcctacc acacacgtga agtccagctc 1380 ttcgtgatcg acaacggcgc ggatgactgg cggatagcca tgacctacga gcgcatcctg 1440 tacatcagcc tggagatgct ggtgtgcgcc atccacccca ttcctggcga gtacaagttc 1500 ttctggacgg cacgcctggc cttctcctac acaccctccc gggcggaggc cgatgtggac 1560 atcatcctgt ctatccccat gttcctgcgc ctgtacctga tcgcccgagt catgctgctg 1620 cacagcaagc tcttcaccga tgcctcgtcc cgcagcatcg gggccctcaa caagatcaac 1680 ttcaacaccc gctttgtcat gaagacgctc atgaccatct gccctggcac tgtgctgctc 1740 gtgttcagca tctctctgtg gatcattgct gcctggaccg tccgtgtctg tgaaaggtac 1800 catgaccagc aggacgtaac tagtaacttt ctgggtgcca tgtggctcat ctccatcaca 1860 ttcctttcca ttggttatgg ggacatggtg ccccacacat actgtgggaa aggtgtctgt 1920 ctcctcactg gcatcatggg tgcaggctgc actgcccttg tggtggccgt ggtggcccga 1980 aagctggaac tcaccaaagc ggagaagcac gttcataact tcatgatgga cactcagctc 2040 accaagcgga tcaagaatgc tgcagccaat gtccttcggg aaacatggtt aatctataaa 2100 cacacaaagc tgctaaagaa gattgaccat gccaaagtga ggaaacacca gaggaagttc 2160 ctccaagcta tccaccagtt gaggagcgtc aagatggaac agaggaagct gagtgaccaa 2220 gccaacactc tggtggacct ttccaagatg cagaatgtca tgtatgactt aatcacagaa 2280 ctcaatgacc ggagcgaaga cctggagaag cagattggca gcctggagtc gaagctggag 2340 catctcaccg ccagcttcaa ctccctgccg ctgctcatcg ccgacaccct gcgccagcag 2400 cagcagcagc tcctgtctgc catcatcgag gcccggggtg tcagcgtggc agtgggcacc 2460 acccacaccc caatctccga tagccccatt ggggtcagct ccacctcctt cccgaccccg 2520 tacacaagtt caagcagttg ctaaataaat ctccccactc cagaagcatt acccataggt 2580 cttaagatgc aaatcaactc tctcctggtc gctttgccat caagaaacat tcagaccagg 2640 gaacggaaag aagagagacc gagctaatta actaactcat gttcattcag cgtgcttggt 2700 ccgacatgcc ttgaaaccag aaatctaatc tctgtttagg tgcctctact tgggagcggg 2760 aagaggagat gacaggaagc gacgcctctg gcagggccct tgctgcagag ttggtggaga 2820 acagaaatcc acgctcaatc tcaggtcttc acgcgggggg tgggggtcag atgcactgaa 2880 gtagccaaca gcgaaaccag tccagaagag gggtccgctg ggagggaggg ttgtgtcagg 2940 cttgggggat gggctcttcg ccatgggggt ctttgaacac acctctctcc tttccttttg 3000 tctacggaag cctctgggtg acaaaagtaa aagagagctg cccacaactt gccaaaacag 3060 atatactcga atcagactga aaaaaaaaaa aaaaa 3095 98 736 PRT Homo Sapiens 98 Met Asp Thr Ser Gly His Phe His Asp Ser Gly Val Gly Asp Leu Asp 1 5 10 15 Glu Asp Pro Lys Cys Pro Cys Pro Ser Ser Gly Asp Glu Gln Gln Gln 20 25 30 Gln Gln Gln Gln Gln Gln Gln Gln Gln Pro Pro Pro Pro Ala Pro Pro 35 40 45 Ala Ala Pro Gln Gln Pro Leu Gly Pro Ser Leu Gln Pro Gln Pro Pro 50 55 60 Gln Leu Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln Gln 65 70 75 80 Gln Gln Gln Gln Gln Pro Pro His Pro Leu Ser Gln Leu Ala Gln Leu 85 90 95 Gln Ser Gln Pro Val His Pro Gly Leu Leu His Ser Ser Pro Thr Ala 100 105 110 Phe Arg Ala Pro Pro Ser Ser Asn Ser Thr Ala Ile Leu His Pro Ser 115 120 125 Ser Arg Gln Gly Ser Gln Leu Asn Leu Asn Asp His Leu Leu Gly His 130 135 140 Ser Pro Ser Ser Thr Ala Thr Ser Gly Pro Gly Gly Gly Ser Arg His 145 150 155 160 Arg Gln Ala Ser Pro Leu Val His Arg Arg Asp Ser Asn Pro Phe Thr 165 170 175 Glu Ile Ala Met Ser Ser Cys Lys Tyr Ser Gly Gly Val Met Lys Pro 180 185 190 Leu Ser Arg Leu Ser Ala Ser Arg Arg Asn Leu Ile Glu Ala Glu Thr 195 200 205 Glu Gly Gln Pro Leu Gln Leu Phe Ser Pro Ser Asn Pro Pro Glu Ile 210 215 220 Val Ile Ser Ser Arg Glu Asp Asn His Ala His Gln Thr Leu Leu His 225 230 235 240 His Pro Asn Ala Thr His Asn His Gln His Ala Gly Thr Thr Ala Ser 245 250 255 Ser Thr Thr Phe Pro Lys Ala Asn Lys Arg Lys Asn Gln Asn Ile Gly 260 265 270 Tyr Lys Leu Gly His Arg Arg Ala Leu Phe Glu Lys Arg Lys Arg Leu 275 280 285 Ser Asp Tyr Ala Leu Ile Phe Gly Met Phe Gly Ile Val Val Met Val 290 295 300 Ile Glu Thr Glu Leu Ser Trp Gly Leu Tyr Ser Lys Asp Ser Met Phe 305 310 315 320 Ser Leu Ala Leu Lys Cys Leu Ile Ser Leu Ser Thr Ile Ile Leu Leu 325 330 335 Gly Leu Ile Ile Ala Tyr His Thr Arg Glu Val Gln Leu Phe Val Ile 340 345 350 Asp Asn Gly Ala Asp Asp Trp Arg Ile Ala Met Thr Tyr Glu Arg Ile 355 360 365 Leu Tyr Ile Ser Leu Glu Met Leu Val Cys Ala Ile His Pro Ile Pro 370 375 380 Gly Glu Tyr Lys Phe Phe Trp Thr Ala Arg Leu Ala Phe Ser Tyr Thr 385 390 395 400 Pro Ser Arg Ala Glu Ala Asp Val Asp Ile Ile Leu Ser Ile Pro Met 405 410 415 Phe Leu Arg Leu Tyr Leu Ile Ala Arg Val Met Leu Leu His Ser Lys 420 425 430 Leu Phe Thr Asp Ala Ser Ser Arg Ser Ile Gly Ala Leu Asn Lys Ile 435 440 445 Asn Phe Asn Thr Arg Phe Val Met Lys Thr Leu Met Thr Ile Cys Pro 450 455 460 Gly Thr Val Leu Leu Val Phe Ser Ile Ser Leu Trp Ile Ile Ala Ala 465 470 475 480 Trp Thr Val Arg Val Cys Glu Arg Tyr His Asp Gln Gln Asp Val Thr 485 490 495 Ser Asn Phe Leu Gly Ala Met Trp Leu Ile Ser Ile Thr Phe Leu Ser 500 505 510 Ile Gly Tyr Gly Asp Met Val Pro His Thr Tyr Cys Gly Lys Gly Val 515 520 525 Cys Leu Leu Thr Gly Ile Met Gly Ala Gly Cys Thr Ala Leu Val Val 530 535 540 Ala Val Val Ala Arg Lys Leu Glu Leu Thr Lys Ala Glu Lys His Val 545 550 555 560 His Asn Phe Met Met Asp Thr Gln Leu Thr Lys Arg Ile Lys Asn Ala 565 570 575 Ala Ala Asn Val Leu Arg Glu Thr Trp Leu Ile Tyr Lys His Thr Lys 580 585 590 Leu Leu Lys Lys Ile Asp His Ala Lys Val Arg Lys His Gln Arg Lys 595 600 605 Phe Leu Gln Ala Ile His Gln Leu Arg Ser Val Lys Met Glu Gln Arg 610 615 620 Lys Leu Ser Asp Gln Ala Asn Thr Leu Val Asp Leu Ser Lys Met Gln 625 630 635 640 Asn Val Met Tyr Asp Leu Ile Thr Glu Leu Asn Asp Arg Ser Glu Asp 645 650 655 Leu Glu Lys Gln Ile Gly Ser Leu Glu Ser Lys Leu Glu His Leu Thr 660 665 670 Ala Ser Phe Asn Ser Leu Pro Leu Leu Ile Ala Asp Thr Leu Arg Gln 675 680 685 Gln Gln Gln Gln Leu Leu Ser Ala Ile Ile Glu Ala Arg Gly Val Ser 690 695 700 Val Ala Val Gly Thr Thr His Thr Pro Ile Ser Asp Ser Pro Ile Gly 705 710 715 720 Val Ser Ser Thr Ser Phe Pro Thr Pro Tyr Thr Ser Ser Ser Ser Cys 725 730 735 99 2393 DNA Homo Sapiens 99 cgcccgggca ggttgagaag ccaggggcca agatggatct tctcctcgac atcagctaag 60 cctggaggac tcttcccctc agagaccatg gagagggaca gccacgggaa tgcatctcca 120 gcaagaacac cttcagctgg agcatctcca gcccaggcat ctccagctgg gacacctcca 180 ggccgggcat ctccagccca ggcatctcca gcccaggcat ctccagctgg gacacctccg 240 ggccgggcat ctccagccca ggcatctcca gctggtacac ctccaggccg ggcatctcca 300 ggccgggcat ctccagccca ggcatctcca gcccgggcat ctccggctct ggcatcactt 360 tccaggtcct catccggcag gtcatcatcc gccaggtcag cctcggtgac aacctcccca 420 accagagtgt accttgttag agcaacacca gtgggggctg tacccatccg atcatctcct 480 gccaggtcag caccagcaac cagggccacc agggagagcc caggtacgag cctgcccaag 540 ttcacctggc gggagggcca gaagcagcta ccgctcatcg ggtgcgtgct cctcctcatt 600 gccctggtgg tttcgctcat catcctcttc cagttctggc agggccacac agggatcagg 660 cacaaggagc agagggagag ctgtcccaag cacgctgttc gctgtgacgg ggtggtggac 720 tgcaagctga agagtgacga gctgggctgc gtgaggtttg actgggacaa gtctctgctt 780 aaaatctact ctgggtcctc ccatcagtgg cttcccatct gtagcagcaa ctggaatgac 840 tcctactcag agaagacctg ccagcagctg ggtttcgaga gtgctcaccg gacaaccgag 900 gttgcccaca gggattttgc caacagcttc tcaatcttga gatacaactc caccatccag 960 gaaagcctcc acaggtctga atgcccttcc cagcggtata tctccctcca gtgttcccac 1020 tgcggactga gggccatgac cgggcggatc gtgggagggg cgctggcctc ggatagcaag 1080 tggccttggc aagtgagtct gcacttcggc accacccaca tctgtggagg cacgctcatt 1140 gacgcccagt gggtgctcac tgccgcccac tgcttcttcg tgacccggga gaaggtcctg 1200 gagggctgga aggtgtacgc gggcaccagc aacctgcacc agttgcctga ggcagcctcc 1260 attgccgaga tcatcatcaa cagcaattac accgatgagg aggacgacta tgacatcgcc 1320 ctcatgcggc tgtccaagcc cctgaccctg tccgctcaca tccaccctgc ttgcctcccc 1380 atgcatggac agacctttag cctcaatgag acctgctgga tcacaggctt tggcaagacc 1440 agggagacag atgacaagac atcccccttc ctccgggagg tgcaggtcaa tctcatcgac 1500 ttcaagaaat gcaatgacta cttggtctat gacagttacc ttaccccaag gatgatgtgt 1560 gctggggacc ttcgtggggg cagagactcc tgccagggag acagcggggg gcctcttgtc 1620 tgtgagcaga acaaccgctg gtacctggca ggtgtcacca gctggggcac aggctgtggc 1680 cagagaaaca aacctggtgt gtacaccaaa gtgacagaag ttcttccctg gatttacagc 1740 aagatggagg taagatccct gcagcaggac actgcaccca gcaggctggg aacttcctca 1800 ggtggggacc ctggaggagc acccagggtg taggcagagg tcccctcagc gtccccatat 1860 tcggggggtg ttctggacag ggtcaaatgt gatgcctggg gtcaatccca gctgtctgtg 1920 tttctttccc tgcttttctt ccctcagaac agagctcagc gggttgaaaa agggtggacc 1980 tacaggccag gcaggcagtt gctgggcaga tgttctccca gaagtatttt tttgtgtaag 2040 gttgcaatgg actttgaaaa cgtttcagtt tctgcagagg attttgtgat agtctttgtt 2100 atcaagcatt tatgcatggg aatccgctct tcatggcctt tcccagctct gtttgtttta 2160 gtctttttga ttttcttttt gttgttgttg ttgtcttttt ttaaaaacac aagtgactcc 2220 attttaactc tgacaacttt cacagctgtc accagaatgc tccctgagaa ctaccattct 2280 ttccctttcc cacttaaaat atttcatcag aacctcacca ctatcataaa agagtataaa 2340 gtaataaaat aataaaaagc gaaaaaaaaa aaaaaaaaaa aaaaaaaaaa aaa 2393 100 581 PRT Homo Sapiens 100 Met Glu Arg Asp Ser His Gly Asn Ala Ser Pro Ala Arg Thr Pro Ser 1 5 10 15 Ala Gly Ala Ser Pro Ala Gln Ala Ser Pro Ala Gly Thr Pro Pro Gly 20 25 30 Arg Ala Ser Pro Ala Gln Ala Ser Pro Ala Gln Ala Ser Pro Ala Gly 35 40 45 Thr Pro Pro Gly Arg Ala Ser Pro Ala Gln Ala Ser Pro Ala Gly Thr 50 55 60 Pro Pro Gly Arg Ala Ser Pro Gly Arg Ala Ser Pro Ala Gln Ala Ser 65 70 75 80 Pro Ala Arg Ala Ser Pro Ala Leu Ala Ser Leu Ser Arg Ser Ser Ser 85 90 95 Gly Arg Ser Ser Ser Ala Arg Ser Ala Ser Val Thr Thr Ser Pro Thr 100 105 110 Arg Val Tyr Leu Val Arg Ala Thr Pro Val Gly Ala Val Pro Ile Arg 115 120 125 Ser Ser Pro Ala Arg Ser Ala Pro Ala Thr Arg Ala Thr Arg Glu Ser 130 135 140 Pro Gly Thr Ser Leu Pro Lys Phe Thr Trp Arg Glu Gly Gln Lys Gln 145 150 155 160 Leu Pro Leu Ile Gly Cys Val Leu Leu Leu Ile Ala Leu Val Val Ser 165 170 175 Leu Ile Ile Leu Phe Gln Phe Trp Gln Gly His Thr Gly Ile Arg His 180 185 190 Lys Glu Gln Arg Glu Ser Cys Pro Lys His Ala Val Arg Cys Asp Gly 195 200 205 Val Val Asp Cys Lys Leu Lys Ser Asp Glu Leu Gly Cys Val Arg Phe 210 215 220 Asp Trp Asp Lys Ser Leu Leu Lys Ile Tyr Ser Gly Ser Ser His Gln 225 230 235 240 Trp Leu Pro Ile Cys Ser Ser Asn Trp Asn Asp Ser Tyr Ser Glu Lys 245 250 255 Thr Cys Gln Gln Leu Gly Phe Glu Ser Ala His Arg Thr Thr Glu Val 260 265 270 Ala His Arg Asp Phe Ala Asn Ser Phe Ser Ile Leu Arg Tyr Asn Ser 275 280 285 Thr Ile Gln Glu Ser Leu His Arg Ser Glu Cys Pro Ser Gln Arg Tyr 290 295 300 Ile Ser Leu Gln Cys Ser His Cys Gly Leu Arg Ala Met Thr Gly Arg 305 310 315 320 Ile Val Gly Gly Ala Leu Ala Ser Asp Ser Lys Trp Pro Trp Gln Val 325 330 335 Ser Leu His Phe Gly Thr Thr His Ile Cys Gly Gly Thr Leu Ile Asp 340 345 350 Ala Gln Trp Val Leu Thr Ala Ala His Cys Phe Phe Val Thr Arg Glu 355 360 365 Lys Val Leu Glu Gly Trp Lys Val Tyr Ala Gly Thr Ser Asn Leu His 370 375 380 Gln Leu Pro Glu Ala Ala Ser Ile Ala Glu Ile Ile Ile Asn Ser Asn 385 390 395 400 Tyr Thr Asp Glu Glu Asp Asp Tyr Asp Ile Ala Leu Met Arg Leu Ser 405 410 415 Lys Pro Leu Thr Leu Ser Ala His Ile His Pro Ala Cys Leu Pro Met 420 425 430 His Gly Gln Thr Phe Ser Leu Asn Glu Thr Cys Trp Ile Thr Gly Phe 435 440 445 Gly Lys Thr Arg Glu Thr Asp Asp Lys Thr Ser Pro Phe Leu Arg Glu 450 455 460 Val Gln Val Asn Leu Ile Asp Phe Lys Lys Cys Asn Asp Tyr Leu Val 465 470 475 480 Tyr Asp Ser Tyr Leu Thr Pro Arg Met Met Cys Ala Gly Asp Leu Arg 485 490 495 Gly Gly Arg Asp Ser Cys Gln Gly Asp Ser Gly Gly Pro Leu Val Cys 500 505 510 Glu Gln Asn Asn Arg Trp Tyr Leu Ala Gly Val Thr Ser Trp Gly Thr 515 520 525 Gly Cys Gly Gln Arg Asn Lys Pro Gly Val Tyr Thr Lys Val Thr Glu 530 535 540 Val Leu Pro Trp Ile Tyr Ser Lys Met Glu Val Arg Ser Leu Gln Gln 545 550 555 560 Asp Thr Ala Pro Ser Arg Leu Gly Thr Ser Ser Gly Gly Asp Pro Gly 565 570 575 Gly Ala Pro Arg Val 580 101 2263 DNA Homo Sapiens 101 agccagaggg acgagctagc ccgacgatgg cccaggggac attgatccgt gtgaccccag 60 agcagcccac ccatgccgtg tgtgtgctgg gcaccttgac tcagcttgac atctgcagct 120 ctgcccctga ggactgcacg tccttcagca tcaacgcctc cccaggggtg gtcgtggata 180 ttgcccacag ccctccagcc aagaagaaat ccacaggttc ctccacatgg cccctggacc 240 ctggggtaga ggtgaccctg acgatgaaag cggccagtgg tagcacaggc gaccagaagg 300 ttcagatttc atactacgga cccaagactc caccagtcaa agctctactc tacctcaccg 360 cggtggaaat ctccctgtgc gcagacatca cccgcaccgg caaagtgaag ccaaccagag 420 ctgtgaaaga tcagaggacc tggacctggg gcccttgtgg acagggtgcc atcctgctgg 480 tgaactgtga cagagacaat ctcgaatctt ctgccatgga ctgcgaggat gatgaagtgc 540 ttgacagcga agacctgcag gacatgtcgc tgatgaccct gagcacgaag acccccaagg 600 acttcttcac aaaccataca ctggtgctcc acgtggccag gtctgagatg gacaaagtga 660 gggtgtttca ggccacacgg ggcaaactgt cctccaagtg cagcgtagtc ttgggtccca 720 agtggccctc tcactacctg atggtccccg gtggaaagca caacatggac ttctacgtgg 780 aggccctcgc tttcccggac accgacttcc cggggctcat taccctcacc atctccctgc 840 tggacacgtc caacctggag ctccccgagg ctgtggtgtt ccaagacagc gtggtcttcc 900 gcgtggcgcc ctggatcatg acccccaaca cccagccccc gcaggaggtg tacgcgtgca 960 gtatttttga aaatgaggac ttcctgaagt cagtgactac tctggccatg aaagccaagt 1020 gcaagctgac catctgccct gaggaggaga acatggatga ccagtggatg caggatgaaa 1080 tggagatcgg ctacatccaa gccccacaca aaacgctgcc cgtggtcttc gactctccaa 1140 ggaacagagg cctgaaggag tttcccatca aacgagtgat gggtccagat tttggctatg 1200 taactcgagg gccccaaaca gggggtatca gtggactgga ctcctttggg aacctggaag 1260 tgagcccccc agtcacagtc aggggcaagg aatacccgct gggcaggatt ctcttcgggg 1320 acagctgtta tcccagcaat gacagccggc agatgcacca ggccctgcag gacttcctca 1380 gtgcccagca ggtgcaggcc cctgtgaagc tctattctga ctggctgtcc gtgggccacg 1440 tggacgagtt cctgagcttt gtgccagcac ccgacaggaa gggcttccgg ctgctcctgg 1500 ccagccccag gtcctgctac aaactgttcc aggagcagca gaatgagggc cacggggagg 1560 ccctgctgtt cgaagggatc aagaaaaaaa aacagcagaa aataaagaac attctgtcaa 1620 acaagacatt gagagaacat aattcatttg tggagagatg catcgactgg aaccgcgagc 1680 tgctgaagcg ggagctgggc ctggccgaga gtgacatcat tgacatcccg cagctcttca 1740 agctcaaaga gttctctaag gcggaagctt ttttccccaa catggtgaac atgctggtgc 1800 tagggaagca cctgggcatc cccaagccct tcgggcccgt catcaacggc cgctgctgcc 1860 tggaggagaa ggtgtgttcc ctgctggagc cactgggcct ccagtgcacc ttcatcaacg 1920 acttcttcac ctaccacatc aggcatgggg aggtgcactg cggcaccaac gtgcgcagaa 1980 agcccttctc cttcaagtgg tggaacatgg tgccctgagc ccatcttccc tggcgtcctc 2040 tccctcctgg ccagatgtcg ctgggtcctc tgcagtgtgg caagcaagag ctcttgtgaa 2100 tattgtggct ccctgggggc ggccagccct cccagcagtg gcttgctttc ttctcctgtg 2160 atgtcccagt ttcccactct gaagatccca acatggtcct agcactgcac actcagttct 2220 gctctaagaa gctgcaataa agttttttta agtcactttg tac 2263 102 663 PRT Homo Sapiens 102 Met Ala Gln Gly Thr Leu Ile Arg Val Thr Pro Glu Gln Pro Thr His 1 5 10 15 Ala Val Cys Val Leu Gly Thr Leu Thr Gln Leu Asp Ile Cys Ser Ser 20 25 30 Ala Pro Glu Asp Cys Thr Ser Phe Ser Ile Asn Ala Ser Pro Gly Val 35 40 45 Val Val Asp Ile Ala His Ser Pro Pro Ala Lys Lys Lys Ser Thr Gly 50 55 60 Ser Ser Thr Trp Pro Leu Asp Pro Gly Val Glu Val Thr Leu Thr Met 65 70 75 80 Lys Ala Ala Ser Gly Ser Thr Gly Asp Gln Lys Val Gln Ile Ser Tyr 85 90 95 Tyr Gly Pro Lys Thr Pro Pro Val Lys Ala Leu Leu Tyr Leu Thr Ala 100 105 110 Val Glu Ile Ser Leu Cys Ala Asp Ile Thr Arg Thr Gly Lys Val Lys 115 120 125 Pro Thr Arg Ala Val Lys Asp Gln Arg Thr Trp Thr Trp Gly Pro Cys 130 135 140 Gly Gln Gly Ala Ile Leu Leu Val Asn Cys Asp Arg Asp Asn Leu Glu 145 150 155 160 Ser Ser Ala Met Asp Cys Glu Asp Asp Glu Val Leu Asp Ser Glu Asp 165 170 175 Leu Gln Asp Met Ser Leu Met Thr Leu Ser Thr Lys Thr Pro Lys Asp 180 185 190 Phe Phe Thr Asn His Thr Leu Val Leu His Val Ala Arg Ser Glu Met 195 200 205 Asp Lys Val Arg Val Phe Gln Ala Thr Arg Gly Lys Leu Ser Ser Lys 210 215 220 Cys Ser Val Val Leu Gly Pro Lys Trp Pro Ser His Tyr Leu Met Val 225 230 235 240 Pro Gly Gly Lys His Asn Met Asp Phe Tyr Val Glu Ala Leu Ala Phe 245 250 255 Pro Asp Thr Asp Phe Pro Gly Leu Ile Thr Leu Thr Ile Ser Leu Leu 260 265 270 Asp Thr Ser Asn Leu Glu Leu Pro Glu Ala Val Val Phe Gln Asp Ser 275 280 285 Val Val Phe Arg Val Ala Pro Trp Ile Met Thr Pro Asn Thr Gln Pro 290 295 300 Pro Gln Glu Val Tyr Ala Cys Ser Ile Phe Glu Asn Glu Asp Phe Leu 305 310 315 320 Lys Ser Val Thr Thr Leu Ala Met Lys Ala Lys Cys Lys Leu Thr Ile 325 330 335 Cys Pro Glu Glu Glu Asn Met Asp Asp Gln Trp Met Gln Asp Glu Met 340 345 350 Glu Ile Gly Tyr Ile Gln Ala Pro His Lys Thr Leu Pro Val Val Phe 355 360 365 Asp Ser Pro Arg Asn Arg Gly Leu Lys Glu Phe Pro Ile Lys Arg Val 370 375 380 Met Gly Pro Asp Phe Gly Tyr Val Thr Arg Gly Pro Gln Thr Gly Gly 385 390 395 400 Ile Ser Gly Leu Asp Ser Phe Gly Asn Leu Glu Val Ser Pro Pro Val 405 410 415 Thr Val Arg Gly Lys Glu Tyr Pro Leu Gly Arg Ile Leu Phe Gly Asp 420 425 430 Ser Cys Tyr Pro Ser Asn Asp Ser Arg Gln Met His Gln Ala Leu Gln 435 440 445 Asp Phe Leu Ser Ala Gln Gln Val Gln Ala Pro Val Lys Leu Tyr Ser 450 455 460 Asp Trp Leu Ser Val Gly His Val Asp Glu Phe Leu Ser Phe Val Pro 465 470 475 480 Ala Pro Asp Arg Lys Gly Phe Arg Leu Leu Leu Ala Ser Pro Arg Ser 485 490 495 Cys Tyr Lys Leu Phe Gln Glu Gln Gln Asn Glu Gly His Gly Glu Ala 500 505 510 Leu Leu Phe Glu Gly Ile Lys Lys Lys Lys Gln Gln Lys Ile Lys Asn 515 520 525 Ile Leu Ser Asn Lys Thr Leu Arg Glu His Asn Ser Phe Val Glu Arg 530 535 540 Cys Ile Asp Trp Asn Arg Glu Leu Leu Lys Arg Glu Leu Gly Leu Ala 545 550 555 560 Glu Ser Asp Ile Ile Asp Ile Pro Gln Leu Phe Lys Leu Lys Glu Phe 565 570 575 Ser Lys Ala Glu Ala Phe Phe Pro Asn Met Val Asn Met Leu Val Leu 580 585 590 Gly Lys His Leu Gly Ile Pro Lys Pro Phe Gly Pro Val Ile Asn Gly 595 600 605 Arg Cys Cys Leu Glu Glu Lys Val Cys Ser Leu Leu Glu Pro Leu Gly 610 615 620 Leu Gln Cys Thr Phe Ile Asn Asp Phe Phe Thr Tyr His Ile Arg His 625 630 635 640 Gly Glu Val His Cys Gly Thr Asn Val Arg Arg Lys Pro Phe Ser Phe 645 650 655 Lys Trp Trp Asn Met Val Pro 660 103 1204 DNA Homo Sapiens 103 gtcgacccac gcgtccgcgt ggatatggag ctggctgctg ccaagtccgg ggcccgcgcc 60 gctgcctagc gcgtcctggg gactctgtgg ggacgcgccc cgcgccgcgg ctcggggacc 120 cgtagagccc ggcgctgcgc gcatggccct gctctcgcgc cccgcgctca ccctcctgct 180 cctcctcatg gccgctgttg tcaggtgcca ggagcaggcc cagaccaccg actggagagc 240 caccctgaag accatccgga acggcgttca taagatagac acgtacctga acgccgcctt 300 ggacctcctg ggaggcgagg acggtctctg ccagtataaa tgcagtgacg gatctaagcc 360 tttcccacgt tatggttata aaccctcccc accgaatgga tgtggctctc cactgtttgg 420 tgttcatctt aacattggta tcccttccct gacaaagtgt tgcaaccaac acgacaggtg 480 ctatgagacc tgtggcaaaa gcaagaatga ctgtgatgaa gaattccagt attgcctctc 540 caagatctgc cgagatgtac agaaaacact aggactaact cagcatgttc aggcatgtga 600 aacaacagtg gagctcttgt ttgacagtgt tatacattta ggttgtaaac catatctgga 660 cagccaacga gccgcatgca ggtgtcatta tgaagaaaaa actgatcttt aaaggagatg 720 ccgacagcta gtgacagatg aagatggaag aacatacctt tgacaaataa ctaatgtttt 780 tacaacataa aactgtctta tttttgtgaa aggattattt tgagacctta aaataattta 840 tatcttgatg ttaaaacctc aaagcaaaaa aagtgaggga gatagtgagg ggagggcacg 900 cttgtcttct caggtatctt ccccagcatt gctcccttac ttagtatgcc aaatgtcttg 960 accaatatca aaaacaagtg cttgtttagc ggagaatttt gaaaagagga atatataact 1020 caattttcac aaccacattt accaaaaaaa gagatcaaat ataaaattca tcataatgtc 1080 tgttcaacat tatcttattt ggaaaatggg gaaattatca cttacaagta tttgtttact 1140 atgaaatttt aaatacacat ttatgcctag aaaaaaaaaa aaaaaaaaaa aaagggcggc 1200 cgct 1204 104 189 PRT Homo Sapiens 104 Met Ala Leu Leu Ser Arg Pro Ala Leu Thr Leu Leu Leu Leu Leu Met 1 5 10 15 Ala Ala Val Val Arg Cys Gln Glu Gln Ala Gln Thr Thr Asp Trp Arg 20 25 30 Ala Thr Leu Lys Thr Ile Arg Asn Gly Val His Lys Ile Asp Thr Tyr 35 40 45 Leu Asn Ala Ala Leu Asp Leu Leu Gly Gly Glu Asp Gly Leu Cys Gln 50 55 60 Tyr Lys Cys Ser Asp Gly Ser Lys Pro Phe Pro Arg Tyr Gly Tyr Lys 65 70 75 80 Pro Ser Pro Pro Asn Gly Cys Gly Ser Pro Leu Phe Gly Val His Leu 85 90 95 Asn Ile Gly Ile Pro Ser Leu Thr Lys Cys Cys Asn Gln His Asp Arg 100 105 110 Cys Tyr Glu Thr Cys Gly Lys Ser Lys Asn Asp Cys Asp Glu Glu Phe 115 120 125 Gln Tyr Cys Leu Ser Lys Ile Cys Arg Asp Val Gln Lys Thr Leu Gly 130 135 140 Leu Thr Gln His Val Gln Ala Cys Glu Thr Thr Val Glu Leu Leu Phe 145 150 155 160 Asp Ser Val Ile His Leu Gly Cys Lys Pro Tyr Leu Asp Ser Gln Arg 165 170 175 Ala Ala Cys Arg Cys His Tyr Glu Glu Lys Thr Asp Leu 180 185 105 1637 DNA Homo Sapiens 105 aagaactggc ctgtacattt tcaaggaatt cttgagaggt tcttggagag attctgggag 60 ccaaacactc cattgggatc ctagctgttt tagagaacaa cttgtaatgg agccttcatc 120 tcttgagctg ccggctgaca cagtgcagcg cattgcggct gaactcaaat gccacccaac 180 ggatgagagg gtggctctcc acctagatga ggaagataag ctgaggcact tcagggagtg 240 cttttatatt cccaaaatac aggatctgcc tccagttgat ttatcattag tgaataaaga 300 tgaaaatgcc atctatttct tgggaaattc tcttggcctt caaccaaaaa tggttaaaac 360 atatcttgaa gaagaactag ataagtgggc caaaatagca gcctatggtc atgaagtggg 420 gaagcgtcct tggattacag gagatgagag tattgtaggc cttatgaagg acattgtagg 480 agccaatgag aaagaaatag ccctaatgaa tgctttgact gtaaatttac atcttctaat 540 gttatcattt tttaagccta cgccaaaacg atataaaatt cttctagaag ccaaagcctt 600 cccttctgat cattatgcta ttgagtcaca actacaactt cacggactta acattgaaga 660 aagtatgcgg atgataaagc caagagaggg ggaagaaacc ttaagaatag aggatatcct 720 tgaagtaatt gagaaggaag gagactcaat tgcagtgatc ctgttcagtg gggtgcattt 780 ttacactgga cagcacttta atattcctgc catcacaaaa gctggacaag cgaagggttg 840 ttatgttggc tttgatctag cacatgcagt tggaaatgtt gaactctact tacatgactg 900 gggagttgat tttgcctgct ggtgttccta caagtattta aatgcaggag caggaggaat 960 tgctggtgcc ttcattcatg aaaagcatgc ccatacgatt aaacctgcat tagtgggatg 1020 gtttggccat gaactcagca ccagatttaa gatggataac aaactgcagt taatccctgg 1080 ggtctgtgga ttccgaattt caaatcctcc cattttgttg gtctgttcct tgcatgctag 1140 tttagagatc tttaagcaag cgacaatgaa ggcattgcgg aaaaaatctg ttttgctaac 1200 tggctatctg gaatacctga tcaagcataa ctatggcaaa gataaagcag caaccaagaa 1260 accagttgtg aacataatta ctccgtctca tgtagaggag cgggggtgcc agctaacaat 1320 aacattttct gttccaaaca aagatgtttt ccaagaacta gaaaaaagag gagtggtttg 1380 tgacaagcgg aatccaaatg gcattcgagt ggctccagtt cctctctata attctttcca 1440 tgatgtttat aaatttacca atctgctcac ttctatactt gactctgcag aaacaaaaaa 1500 ttagcagtgt tttctagaac aacttaagca aattatactg aaagctgctg tggttatttc 1560 agtattattc gatttttaat tattgaaagt atgtcaccat tgaccacatg taactaacaa 1620 taaataatat accttac 1637 106 465 PRT Homo Sapiens 106 Met Glu Pro Ser Ser Leu Glu Leu Pro Ala Asp Thr Val Gln Arg Ile 1 5 10 15 Ala Ala Glu Leu Lys Cys His Pro Thr Asp Glu Arg Val Ala Leu His 20 25 30 Leu Asp Glu Glu Asp Lys Leu Arg His Phe Arg Glu Cys Phe Tyr Ile 35 40 45 Pro Lys Ile Gln Asp Leu Pro Pro Val Asp Leu Ser Leu Val Asn Lys 50 55 60 Asp Glu Asn Ala Ile Tyr Phe Leu Gly Asn Ser Leu Gly Leu Gln Pro 65 70 75 80 Lys Met Val Lys Thr Tyr Leu Glu Glu Glu Leu Asp Lys Trp Ala Lys 85 90 95 Ile Ala Ala Tyr Gly His Glu Val Gly Lys Arg Pro Trp Ile Thr Gly 100 105 110 Asp Glu Ser Ile Val Gly Leu Met Lys Asp Ile Val Gly Ala Asn Glu 115 120 125 Lys Glu Ile Ala Leu Met Asn Ala Leu Thr Val Asn Leu His Leu Leu 130 135 140 Met Leu Ser Phe Phe Lys Pro Thr Pro Lys Arg Tyr Lys Ile Leu Leu 145 150 155 160 Glu Ala Lys Ala Phe Pro Ser Asp His Tyr Ala Ile Glu Ser Gln Leu 165 170 175 Gln Leu His Gly Leu Asn Ile Glu Glu Ser Met Arg Met Ile Lys Pro 180 185 190 Arg Glu Gly Glu Glu Thr Leu Arg Ile Glu Asp Ile Leu Glu Val Ile 195 200 205 Glu Lys Glu Gly Asp Ser Ile Ala Val Ile Leu Phe Ser Gly Val His 210 215 220 Phe Tyr Thr Gly Gln His Phe Asn Ile Pro Ala Ile Thr Lys Ala Gly 225 230 235 240 Gln Ala Lys Gly Cys Tyr Val Gly Phe Asp Leu Ala His Ala Val Gly 245 250 255 Asn Val Glu Leu Tyr Leu His Asp Trp Gly Val Asp Phe Ala Cys Trp 260 265 270 Cys Ser Tyr Lys Tyr Leu Asn Ala Gly Ala Gly Gly Ile Ala Gly Ala 275 280 285 Phe Ile His Glu Lys His Ala His Thr Ile Lys Pro Ala Leu Val Gly 290 295 300 Trp Phe Gly His Glu Leu Ser Thr Arg Phe Lys Met Asp Asn Lys Leu 305 310 315 320 Gln Leu Ile Pro Gly Val Cys Gly Phe Arg Ile Ser Asn Pro Pro Ile 325 330 335 Leu Leu Val Cys Ser Leu His Ala Ser Leu Glu Ile Phe Lys Gln Ala 340 345 350 Thr Met Lys Ala Leu Arg Lys Lys Ser Val Leu Leu Thr Gly Tyr Leu 355 360 365 Glu Tyr Leu Ile Lys His Asn Tyr Gly Lys Asp Lys Ala Ala Thr Lys 370 375 380 Lys Pro Val Val Asn Ile Ile Thr Pro Ser His Val Glu Glu Arg Gly 385 390 395 400 Cys Gln Leu Thr Ile Thr Phe Ser Val Pro Asn Lys Asp Val Phe Gln 405 410 415 Glu Leu Glu Lys Arg Gly Val Val Cys Asp Lys Arg Asn Pro Asn Gly 420 425 430 Ile Arg Val Ala Pro Val Pro Leu Tyr Asn Ser Phe His Asp Val Tyr 435 440 445 Lys Phe Thr Asn Leu Leu Thr Ser Ile Leu Asp Ser Ala Glu Thr Lys 450 455 460 Asn 465 107 1647 DNA Homo Sapiens 107 ggcaggcatg ggagccgcgc gctctctccc ggcgcccaca cctgtctgag cggcgcagcg 60 agccgcggcc cgggcgggct gctcggcgcg gaacagtgct cggcatggca gggattccag 120 ggctcctctt ccttctcttc tttctgctct gtgctgttgg gcaagtgagc ccttacagtg 180 ccccctggaa acccacttgg cctgcatacc gcctccctgt cgtcttgccc cagtctaccc 240 tcaatttagc caagccagac tttggagccg aagccaaatt agaagtatct tcttcatgtg 300 gaccccagtg tcataaggga actccactgc ccacttacga agaggccaag caatatctgt 360 cttatgaaac gctctatgcc aatggcagcc gcacagagac gcaggtgggc atctacatcc 420 tcagcagtag tggagatggg gcccaacacc gagactcagg gtcttcagga aagtctcgaa 480 ggaagcggca gatttatggc tatgacagca ggttcagcat ttttgggaag gacttcctgc 540 tcaactaccc tttctcaaca tcagtgaagt tatccacggg ctgcaccggc accctggtgg 600 cagagaagca tgtcctcaca gctgcccact gcatacacga tggaaaaacc tatgtgaaag 660 gaacccagaa gcttcgagtg ggcttcctaa agcccaagtt taaagatggt ggtcgagggg 720 ccaacgactc cacttcagcc atgcccgagc agatgaaatt tcagtggatc cgggtgaaac 780 gcacccatgt gcccaagggt tggatcaagg gcaatgccaa tgacatcggc atggattatg 840 attatgccct cctggaactc aaaaagcccc acaagagaaa atttatgaag attggggtga 900 gccctcctgc taagcagctg ccagggggca gaattcactt ctctggttat gacaatgacc 960 gaccaggcaa tttggtgtat cgcttctgtg acgtcaaaga cgagacctat gacttgctct 1020 accagcaatg cgatgcccag ccaggggcca gcgggtctgg ggtctatgtg aggatgtgga 1080 agagacagca gcagaagtgg gagcgaaaaa ttattggcat tttttcaggg caccagtggg 1140 tggacatgaa tggttcccca caggatttca acgtggctgt cagaatcact cctctcaaat 1200 atgcccagat ttgctattgg attaaaggaa actacctgga ttgtagggag gggtgacaca 1260 gtgttccctc ctggcagcaa ttaagggtct tcatgttctt attttaggag aggccaaatt 1320 gttttttgtc attggcgtgc acacgtgtgt gtgtgtgtgt gtgtgtgtgt aaggtgtctt 1380 ataatctttt acctatttct tacaattgca agatgactgg ctttactatt tgaaaactgg 1440 tttgtgtatc atatcatata tcatttaagc agtttgaagg catacttttg catagaaata 1500 aaaaaaatac tgatttgggg caatgaggaa tatttgacaa ttaagttaat cttcacgttt 1560 ttgcaaactt tgatttttat ttcatctgaa cttgtttcaa agatttatat taaatatttg 1620 gcatacaaga gaaaaaaaaa aaaaaaa 1647 108 383 PRT Homo Sapiens 108 Met Ala Gly Ile Pro Gly Leu Leu Phe Leu Leu Phe Phe Leu Leu Cys 1 5 10 15 Ala Val Gly Gln Val Ser Pro Tyr Ser Ala Pro Trp Lys Pro Thr Trp 20 25 30 Pro Ala Tyr Arg Leu Pro Val Val Leu Pro Gln Ser Thr Leu Asn Leu 35 40 45 Ala Lys Pro Asp Phe Gly Ala Glu Ala Lys Leu Glu Val Ser Ser Ser 50 55 60 Cys Gly Pro Gln Cys His Lys Gly Thr Pro Leu Pro Thr Tyr Glu Glu 65 70 75 80 Ala Lys Gln Tyr Leu Ser Tyr Glu Thr Leu Tyr Ala Asn Gly Ser Arg 85 90 95 Thr Glu Thr Gln Val Gly Ile Tyr Ile Leu Ser Ser Ser Gly Asp Gly 100 105 110 Ala Gln His Arg Asp Ser Gly Ser Ser Gly Lys Ser Arg Arg Lys Arg 115 120 125 Gln Ile Tyr Gly Tyr Asp Ser Arg Phe Ser Ile Phe Gly Lys Asp Phe 130 135 140 Leu Leu Asn Tyr Pro Phe Ser Thr Ser Val Lys Leu Ser Thr Gly Cys 145 150 155 160 Thr Gly Thr Leu Val Ala Glu Lys His Val Leu Thr Ala Ala His Cys 165 170 175 Ile His Asp Gly Lys Thr Tyr Val Lys Gly Thr Gln Lys Leu Arg Val 180 185 190 Gly Phe Leu Lys Pro Lys Phe Lys Asp Gly Gly Arg Gly Ala Asn Asp 195 200 205 Ser Thr Ser Ala Met Pro Glu Gln Met Lys Phe Gln Trp Ile Arg Val 210 215 220 Lys Arg Thr His Val Pro Lys Gly Trp Ile Lys Gly Asn Ala Asn Asp 225 230 235 240 Ile Gly Met Asp Tyr Asp Tyr Ala Leu Leu Glu Leu Lys Lys Pro His 245 250 255 Lys Arg Lys Phe Met Lys Ile Gly Val Ser Pro Pro Ala Lys Gln Leu 260 265 270 Pro Gly Gly Arg Ile His Phe Ser Gly Tyr Asp Asn Asp Arg Pro Gly 275 280 285 Asn Leu Val Tyr Arg Phe Cys Asp Val Lys Asp Glu Thr Tyr Asp Leu 290 295 300 Leu Tyr Gln Gln Cys Asp Ala Gln Pro Gly Ala Ser Gly Ser Gly Val 305 310 315 320 Tyr Val Arg Met Trp Lys Arg Gln Gln Gln Lys Trp Glu Arg Lys Ile 325 330 335 Ile Gly Ile Phe Ser Gly His Gln Trp Val Asp Met Asn Gly Ser Pro 340 345 350 Gln Asp Phe Asn Val Ala Val Arg Ile Thr Pro Leu Lys Tyr Ala Gln 355 360 365 Ile Cys Tyr Trp Ile Lys Gly Asn Tyr Leu Asp Cys Arg Glu Gly 370 375 380 109 5375 DNA Homo Sapiens 109 gaatctgctg agcccccact aacccagagt gataaaagag agacttctca caccacagca 60 gcagcgactg gtcggagttc ccatgctgat gcaagagaat gtgctatttc aacccaggca 120 gagcaagaag caaaaaccct tcaaacttca acagactcag tctccaaaga aggcaacaca 180 aattgcaagg gagaaggcat gcaagttaat actctatttg aaacaagcca ggttccagac 240 tggagtgatc ctcctcaggt acaagttcag gaaacagtca gagagacaat ctcttgcagc 300 cagatgccag ctttctcaga gcctgctggg gaggagtccc cattcactgg gaccacaaca 360 atttccttct caaacttagg aggggtccac aaggaaaatg catcattagc tcaacactcg 420 gaggtcaaac cctgtacctg tggtccacag caggaagaaa aacaagacag agatggcaac 480 atacctgaca atttcaggga agacctaaaa tatgagcaga gcatctcaga agccaatgat 540 gagactatgt ccccaggtgt gttctcaagg catctcccca aggatgctcg tgctgacttc 600 agggagcctg tggctgtctc tgttgcttcc cctgaaccca cagatactgc cctcaccctg 660 gaaaatgtgt gtgatgagcc aagggacaga gaagcagtgt gtgcaatgga gtgttttgag 720 gctagtgacc aaggaacatg ttttgatacc atagattctc ttgttgggac accagttgat 780 aactattcgc ctcaagaaat ttgctctgta gatacggaac tggcagaagg tcaaaacaaa 840 gtatctgatt tatgttcttc taatgacaag acactggaag tcttttttca gacacaagtg 900 tctgagactt cagtgtctac gtgcaaaagc agcaaggacg gcaactcagt catgtcccct 960 ctttttatca gtactttcac cttgaacatt tcacacacag ctagtgaagg tgccacagga 1020 gaaaatctag ccaaggtgga gaaatccacc tacccactgg cctccacagt acatgctggc 1080 caggagcagc caagccccag caactcagga gggcttgatg aaacacagct cctttcttct 1140 gagaacaatc ctttagtgca atttaaagaa ggaggtgaca agagccccag tcctagtgcc 1200 gcagacacca cagccacacc agccagttat agttcaattg tgagttttcc ttgggagaag 1260 ccaacaacat taactgctaa taatgagtgc tttcaagcga ccagagagac tgttaccatt 1320 gccaccgaag tccacccagc caaatacctt gctgtgtcaa ttcctgagga caagcatgca 1380 ggtggcactg aggagaggtt ccctcgtgca tcccatgaaa aggtttccca atttccttcc 1440 caagtgcagg tggatcatat tttaagtggt gctaccatca aatctacaaa agagctactt 1500 tgcagggcac ccagtgtgcc aggagtccca caccatgtcc tgcagctccc agagggagag 1560 ggtttctgca gtaattcccc tcttcaggtt gataacctgt ctggagataa gagccagact 1620 gtggacagag cagactttag gagctatgaa gagaatttcc aagaaagagg aagtgaaaca 1680 aagcaggggg tccagcagca gagcctgtcc cagcagggtt ctctttctgc acctgatttc 1740 caacaaagtt tgcctacgac atctgctgca caagaggaaa gaaacttggt gcccacggcc 1800 ccctcaccag caagctctag ggaaggagca gggcagcgct caggttgggg gacgagggtc 1860 tccgtggtgg ctgaaactgc tggggaagaa gacagtcagg ctctgagcaa cgttccatct 1920 ctctctgata tccttttgga agagtctaaa gaatatagac ctggaaattg ggaggcaggc 1980 aacaagctga agattataac tctagaggct tccgcttctg aaatctggcc accacgacaa 2040 ctgacaaatt ctgagagcaa ggcatcagac ggtggtctca taattcctga caaggtctgg 2100 gctgtacctg atagtctaaa ggcagatgct gttgtgcctg aattggcccc ctctgaaata 2160 gcagcattgg ctcacagtcc agaggatgct gagtcagccc ttgctgatag cagagaaagc 2220 cataaaggcg aagagcccac catcagtgta cactggagaa gtctttcttc ccggggtttc 2280 agccaaccga gactcctgga gtcatccgtg gaccctgtag atgaaaagga gttatctgtc 2340 acagattcac tgtcagcggc ttctgaaact ggagggaagg aaaatgttaa caatgtgagt 2400 caagaccagg aggaaaaaca actcaagatg gatcacactg ccttctttaa aaagtttctg 2460 acctgcccta aaatcctaga gtcctctgta gatcccattg atgagataag tgtgatagag 2520 tacaccaggg ctggaaaacc agagccctct gaaaccacac cacagggcgc cagagaagga 2580 ggtcaatcaa atgacggaaa catgggccac gaagcggaaa tccagtcggc cattttgcaa 2640 gttccatgtc tccagggaac cattctgagt gaaaatagaa tcagcagaag ccaagaaggc 2700 agtatgaagc aggaggcaga acaaattcaa cctgaggagg caaaaactgc catttggcaa 2760 gtcctgcaac ccagcgaagg cggtgaaaga attccaagtg gatgtagcat aggccaaata 2820 caagaaagca gtgatgggag cttaggggag gctgagcaaa gcaaaaagga caaagcagaa 2880 ttgatttccc ccacttcacc tctttctagt tgtcttccaa taatgactca ctcttctctt 2940 ggggttgaca cgcacaactc cacaggccaa attcatgacg tccctgaaaa tgacatagtt 3000 gagcccagaa agcgtcagta tgtgtttcct gtttcacaga aaaggggaac tattgagaat 3060 gagcgtggga aacctttgcc ctcttctcct gatcttacca ggttcccttg tacttcatct 3120 cctgaaggaa atgtcacaga ctttttgata agccacaaaa tggaggaacc taaaatagag 3180 gtgcttcaaa ttggggaaac caaaccccca agctcatcta gctcctcagc gaagaccttg 3240 gcatttattt caggagaacg tgagttagag aaagccccta agttactgca ggatccatgt 3300 caaaagggca ccctgggctg tgcgaaaaag tccagggaga gagagaagtc cctggaagcc 3360 cgagcaggca aatcgccagg gaccctcaca gcagtgacgg ggtcagagga ggtcaagagg 3420 aagccagaag ccccaggcag tggacattta gctgagggag taaagaagaa aattttgtcc 3480 agggtggcag cactgaggct gaaactggaa gaaaaggaaa atatcagaaa gaactcagcc 3540 tttcttaaaa agatgcccaa actcgaaaca tcattatcac acacagaaga gaaacaagac 3600 ccaaaaaagc catcttgcaa aagagaagga agagctccag tattactgaa aaaaatccaa 3660 gctgagatgt tccctgaaca ctctggaaat gtaaaattaa gctgccaatt tgcagaaatt 3720 catgaagatt ctactatctg ctggacaaaa gattcaaagt ccatagccca agtgcagaga 3780 agtgcagggg acaactccac tgtttccttt gccatcgtgc aagccagtcc gaaggaccag 3840 ggactctatt actgctgcat caagaacagc tacggaaaag tgactgctga atttaacctc 3900 acagctgaag ttctcaaaca gctgtcaagt cgccaggata ctaaaggatg tgaagagatt 3960 gaattcagcc aactcatctt caaagaagac ttcctccatg acagctactt tgggggccgc 4020 ctgcgtggtc agatcgccac ggaggagctg cactttggag aaggggttca ccgcaaagcc 4080 ttccgcagca cagtgatgca cggcctcatg cctgtcttca aacctggcca tgcctgtgtg 4140 cttaaggtgc acaatgccat tgcctatggg accagaaata atgatgagct catccaaagg 4200 aactacaaac tcgctgccca ggaatgctat gttcaaaata ctgccaggta ttatgccaag 4260 atctacgctg ctgaagcaca gcctctggaa ggctttggag aagtacctga gatcattcct 4320 atttttctta tccatcggcc tgagaacaat atcccgtatg ctacagtgga ggaggagctg 4380 attggagaat ttgtgaagta ttccatcagg gatgggaaag aaataaactt cttgagaaga 4440 gaatcagaag ctggtcagaa atgttgcacc ttccagcact gggtgtacca gaaaacaagt 4500 ggctgcctcc tggtgacgga catgcaaggt gtaggaatga agctaactga cgttggcata 4560 gcaacgctgg ctaaagggta caagggattt aaaggcaact gttccatgac cttcattgat 4620 cagtttaaag cactacacca gtgtaacaag tattgcaaaa tgctgggact gaaatccctt 4680 caaaacaaca accagaaaca gaagcagccg agcattggga aaagcaaagt tcaaacaaac 4740 tctatgacag taaagaaggc agggcctgag accccaggcg aaaagaaaac ctaacgtccc 4800 tgggtaacct aatggccact ggctagcagc acacaatctc gccagggaaa atctgaggcc 4860 acacaggaga gaatatacag cctgcagaga gtgcgtggca atccttaccc ccagccgact 4920 gtgcgccaag atgcttctaa acccatcacc tgctgtcttc actcaaatga tttcagaaca 4980 ggatttgcga ccaggtttat ggggagattg aatcaacgat tggtctcaaa gacaggccat 5040 tctttatata cacgtttagc atttttacca acctcacatc atgtgtatat ttgtgtattt 5100 gcacatggtt gtgctgtcga ggacctggtg ctgagaagag tctgttcaca gccaaaattc 5160 ttcccactgt cattcctaac ctgggatttc tagacacatc ctgctgtgat gtaaacagaa 5220 atcacgaatt cgctcactgg atcaagttgt tccactggtg tctaatacgc tattgttgcc 5280 ggaggtgggt tctgtgacgt gaagccattt cccatcattc aacagccagt tacaattttc 5340 tgtttaatta aattcatatt taaacaaaaa aaaaa 5375 110 1531 PRT Homo Sapiens 110 Met Gln Val Asn Thr Leu Phe Glu Thr Ser Gln Val Pro Asp Trp Ser 1 5 10 15 Asp Pro Pro Gln Val Gln Val Gln Glu Thr Val Arg Glu Thr Ile Ser 20 25 30 Cys Ser Gln Met Pro Ala Phe Ser Glu Pro Ala Gly Glu Glu Ser Pro 35 40 45 Phe Thr Gly Thr Thr Thr Ile Ser Phe Ser Asn Leu Gly Gly Val His 50 55 60 Lys Glu Asn Ala Ser Leu Ala Gln His Ser Glu Val Lys Pro Cys Thr 65 70 75 80 Cys Gly Pro Gln Gln Glu Glu Lys Gln Asp Arg Asp Gly Asn Ile Pro 85 90 95 Asp Asn Phe Arg Glu Asp Leu Lys Tyr Glu Gln Ser Ile Ser Glu Ala 100 105 110 Asn Asp Glu Thr Met Ser Pro Gly Val Phe Ser Arg His Leu Pro Lys 115 120 125 Asp Ala Arg Ala Asp Phe Arg Glu Pro Val Ala Val Ser Val Ala Ser 130 135 140 Pro Glu Pro Thr Asp Thr Ala Leu Thr Leu Glu Asn Val Cys Asp Glu 145 150 155 160 Pro Arg Asp Arg Glu Ala Val Cys Ala Met Glu Cys Phe Glu Ala Ser 165 170 175 Asp Gln Gly Thr Cys Phe Asp Thr Ile Asp Ser Leu Val Gly Thr Pro 180 185 190 Val Asp Asn Tyr Ser Pro Gln Glu Ile Cys Ser Val Asp Thr Glu Leu 195 200 205 Ala Glu Gly Gln Asn Lys Val Ser Asp Leu Cys Ser Ser Asn Asp Lys 210 215 220 Thr Leu Glu Val Phe Phe Gln Thr Gln Val Ser Glu Thr Ser Val Ser 225 230 235 240 Thr Cys Lys Ser Ser Lys Asp Gly Asn Ser Val Met Ser Pro Leu Phe 245 250 255 Ile Ser Thr Phe Thr Leu Asn Ile Ser His Thr Ala Ser Glu Gly Ala 260 265 270 Thr Gly Glu Asn Leu Ala Lys Val Glu Lys Ser Thr Tyr Pro Leu Ala 275 280 285 Ser Thr Val His Ala Gly Gln Glu Gln Pro Ser Pro Ser Asn Ser Gly 290 295 300 Gly Leu Asp Glu Thr Gln Leu Leu Ser Ser Glu Asn Asn Pro Leu Val 305 310 315 320 Gln Phe Lys Glu Gly Gly Asp Lys Ser Pro Ser Pro Ser Ala Ala Asp 325 330 335 Thr Thr Ala Thr Pro Ala Ser Tyr Ser Ser Ile Val Ser Phe Pro Trp 340 345 350 Glu Lys Pro Thr Thr Leu Thr Ala Asn Asn Glu Cys Phe Gln Ala Thr 355 360 365 Arg Glu Thr Val Thr Ile Ala Thr Glu Val His Pro Ala Lys Tyr Leu 370 375 380 Ala Val Ser Ile Pro Glu Asp Lys His Ala Gly Gly Thr Glu Glu Arg 385 390 395 400 Phe Pro Arg Ala Ser His Glu Lys Val Ser Gln Phe Pro Ser Gln Val 405 410 415 Gln Val Asp His Ile Leu Ser Gly Ala Thr Ile Lys Ser Thr Lys Glu 420 425 430 Leu Leu Cys Arg Ala Pro Ser Val Pro Gly Val Pro His His Val Leu 435 440 445 Gln Leu Pro Glu Gly Glu Gly Phe Cys Ser Asn Ser Pro Leu Gln Val 450 455 460 Asp Asn Leu Ser Gly Asp Lys Ser Gln Thr Val Asp Arg Ala Asp Phe 465 470 475 480 Arg Ser Tyr Glu Glu Asn Phe Gln Glu Arg Gly Ser Glu Thr Lys Gln 485 490 495 Gly Val Gln Gln Gln Ser Leu Ser Gln Gln Gly Ser Leu Ser Ala Pro 500 505 510 Asp Phe Gln Gln Ser Leu Pro Thr Thr Ser Ala Ala Gln Glu Glu Arg 515 520 525 Asn Leu Val Pro Thr Ala Pro Ser Pro Ala Ser Ser Arg Glu Gly Ala 530 535 540 Gly Gln Arg Ser Gly Trp Gly Thr Arg Val Ser Val Val Ala Glu Thr 545 550 555 560 Ala Gly Glu Glu Asp Ser Gln Ala Leu Ser Asn Val Pro Ser Leu Ser 565 570 575 Asp Ile Leu Leu Glu Glu Ser Lys Glu Tyr Arg Pro Gly Asn Trp Glu 580 585 590 Ala Gly Asn Lys Leu Lys Ile Ile Thr Leu Glu Ala Ser Ala Ser Glu 595 600 605 Ile Trp Pro Pro Arg Gln Leu Thr Asn Ser Glu Ser Lys Ala Ser Asp 610 615 620 Gly Gly Leu Ile Ile Pro Asp Lys Val Trp Ala Val Pro Asp Ser Leu 625 630 635 640 Lys Ala Asp Ala Val Val Pro Glu Leu Ala Pro Ser Glu Ile Ala Ala 645 650 655 Leu Ala His Ser Pro Glu Asp Ala Glu Ser Ala Leu Ala Asp Ser Arg 660 665 670 Glu Ser His Lys Gly Glu Glu Pro Thr Ile Ser Val His Trp Arg Ser 675 680 685 Leu Ser Ser Arg Gly Phe Ser Gln Pro Arg Leu Leu Glu Ser Ser Val 690 695 700 Asp Pro Val Asp Glu Lys Glu Leu Ser Val Thr Asp Ser Leu Ser Ala 705 710 715 720 Ala Ser Glu Thr Gly Gly Lys Glu Asn Val Asn Asn Val Ser Gln Asp 725 730 735 Gln Glu Glu Lys Gln Leu Lys Met Asp His Thr Ala Phe Phe Lys Lys 740 745 750 Phe Leu Thr Cys Pro Lys Ile Leu Glu Ser Ser Val Asp Pro Ile Asp 755 760 765 Glu Ile Ser Val Ile Glu Tyr Thr Arg Ala Gly Lys Pro Glu Pro Ser 770 775 780 Glu Thr Thr Pro Gln Gly Ala Arg Glu Gly Gly Gln Ser Asn Asp Gly 785 790 795 800 Asn Met Gly His Glu Ala Glu Ile Gln Ser Ala Ile Leu Gln Val Pro 805 810 815 Cys Leu Gln Gly Thr Ile Leu Ser Glu Asn Arg Ile Ser Arg Ser Gln 820 825 830 Glu Gly Ser Met Lys Gln Glu Ala Glu Gln Ile Gln Pro Glu Glu Ala 835 840 845 Lys Thr Ala Ile Trp Gln Val Leu Gln Pro Ser Glu Gly Gly Glu Arg 850 855 860 Ile Pro Ser Gly Cys Ser Ile Gly Gln Ile Gln Glu Ser Ser Asp Gly 865 870 875 880 Ser Leu Gly Glu Ala Glu Gln Ser Lys Lys Asp Lys Ala Glu Leu Ile 885 890 895 Ser Pro Thr Ser Pro Leu Ser Ser Cys Leu Pro Ile Met Thr His Ser 900 905 910 Ser Leu Gly Val Asp Thr His Asn Ser Thr Gly Gln Ile His Asp Val 915 920 925 Pro Glu Asn Asp Ile Val Glu Pro Arg Lys Arg Gln Tyr Val Phe Pro 930 935 940 Val Ser Gln Lys Arg Gly Thr Ile Glu Asn Glu Arg Gly Lys Pro Leu 945 950 955 960 Pro Ser Ser Pro Asp Leu Thr Arg Phe Pro Cys Thr Ser Ser Pro Glu 965 970 975 Gly Asn Val Thr Asp Phe Leu Ile Ser His Lys Met Glu Glu Pro Lys 980 985 990 Ile Glu Val Leu Gln Ile Gly Glu Thr Lys Pro Pro Ser Ser Ser Ser 995 1000 1005 Ser Ser Ala Lys Thr Leu Ala Phe Ile Ser Gly Glu Arg Glu Leu Glu 1010 1015 1020 Lys Ala Pro Lys Leu Leu Gln Asp Pro Cys Gln Lys Gly Thr Leu Gly 1025 1030 1035 1040 Cys Ala Lys Lys Ser Arg Glu Arg Glu Lys Ser Leu Glu Ala Arg Ala 1045 1050 1055 Gly Lys Ser Pro Gly Thr Leu Thr Ala Val Thr Gly Ser Glu Glu Val 1060 1065 1070 Lys Arg Lys Pro Glu Ala Pro Gly Ser Gly His Leu Ala Glu Gly Val 1075 1080 1085 Lys Lys Lys Ile Leu Ser Arg Val Ala Ala Leu Arg Leu Lys Leu Glu 1090 1095 1100 Glu Lys Glu Asn Ile Arg Lys Asn Ser Ala Phe Leu Lys Lys Met Pro 1105 1110 1115 1120 Lys Leu Glu Thr Ser Leu Ser His Thr Glu Glu Lys Gln Asp Pro Lys 1125 1130 1135 Lys Pro Ser Cys Lys Arg Glu Gly Arg Ala Pro Val Leu Leu Lys Lys 1140 1145 1150 Ile Gln Ala Glu Met Phe Pro Glu His Ser Gly Asn Val Lys Leu Ser 1155 1160 1165 Cys Gln Phe Ala Glu Ile His Glu Asp Ser Thr Ile Cys Trp Thr Lys 1170 1175 1180 Asp Ser Lys Ser Ile Ala Gln Val Gln Arg Ser Ala Gly Asp Asn Ser 1185 1190 1195 1200 Thr Val Ser Phe Ala Ile Val Gln Ala Ser Pro Lys Asp Gln Gly Leu 1205 1210 1215 Tyr Tyr Cys Cys Ile Lys Asn Ser Tyr Gly Lys Val Thr Ala Glu Phe 1220 1225 1230 Asn Leu Thr Ala Glu Val Leu Lys Gln Leu Ser Ser Arg Gln Asp Thr 1235 1240 1245 Lys Gly Cys Glu Glu Ile Glu Phe Ser Gln Leu Ile Phe Lys Glu Asp 1250 1255 1260 Phe Leu His Asp Ser Tyr Phe Gly Gly Arg Leu Arg Gly Gln Ile Ala 1265 1270 1275 1280 Thr Glu Glu Leu His Phe Gly Glu Gly Val His Arg Lys Ala Phe Arg 1285 1290 1295 Ser Thr Val Met His Gly Leu Met Pro Val Phe Lys Pro Gly His Ala 1300 1305 1310 Cys Val Leu Lys Val His Asn Ala Ile Ala Tyr Gly Thr Arg Asn Asn 1315 1320 1325 Asp Glu Leu Ile Gln Arg Asn Tyr Lys Leu Ala Ala Gln Glu Cys Tyr 1330 1335 1340 Val Gln Asn Thr Ala Arg Tyr Tyr Ala Lys Ile Tyr Ala Ala Glu Ala 1345 1350 1355 1360 Gln Pro Leu Glu Gly Phe Gly Glu Val Pro Glu Ile Ile Pro Ile Phe 1365 1370 1375 Leu Ile His Arg Pro Glu Asn Asn Ile Pro Tyr Ala Thr Val Glu Glu 1380 1385 1390 Glu Leu Ile Gly Glu Phe Val Lys Tyr Ser Ile Arg Asp Gly Lys Glu 1395 1400 1405 Ile Asn Phe Leu Arg Arg Glu Ser Glu Ala Gly Gln Lys Cys Cys Thr 1410 1415 1420 Phe Gln His Trp Val Tyr Gln Lys Thr Ser Gly Cys Leu Leu Val Thr 1425 1430 1435 1440 Asp Met Gln Gly Val Gly Met Lys Leu Thr Asp Val Gly Ile Ala Thr 1445 1450 1455 Leu Ala Lys Gly Tyr Lys Gly Phe Lys Gly Asn Cys Ser Met Thr Phe 1460 1465 1470 Ile Asp Gln Phe Lys Ala Leu His Gln Cys Asn Lys Tyr Cys Lys Met 1475 1480 1485 Leu Gly Leu Lys Ser Leu Gln Asn Asn Asn Gln Lys Gln Lys Gln Pro 1490 1495 1500 Ser Ile Gly Lys Ser Lys Val Gln Thr Asn Ser Met Thr Val Lys Lys 1505 1510 1515 1520 Ala Gly Pro Glu Thr Pro Gly Glu Lys Lys Thr 1525 1530 111 1241 DNA Homo Sapiens 111 cgcctccccc ccccccccag gagcgggggg gaaggactaa caagacgagc gctctggatc 60 ttactaaagg aataagcgtg cggccgcagg gccatgctag ccttgcgcgt ggcgcgcggc 120 tcgtgggggg ccctgcgcgg cgccgcttgg gctccgggaa cgcggccgag taagcgacgc 180 gcctgctggg ccctgctgcc gcccgtgccc tgctgcttgg gctgcctggc cgaacgctgg 240 aggctgcgtc cggccgctct tggcttgcgg ctgcccggga tcggccagcg gaaccactgt 300 tcgggcgcgg ggaaggcggc tcccaggcca gcggccggag cgggcgccgc tgccgaagcc 360 ccgggcggcc agtggggccc ggcgagcacc cccagcctgt atgaaaaccc atggacaatc 420 ccgaatatgt tgtcaatgac gagaattggc ttggccccag ttctgggcta tttgattatt 480 gaagaagatt ttaatattgc actaggagtt tttgctttag ctggactaac agatttgttg 540 gatggattta ttgctcgaaa ctgggccaat caaagatcag ctttgggaag tgctcttgat 600 ccacttgctg ataaaatact tatcagtatc ttatatgtta gcttgaccta tgcagatctt 660 attccagttc cacttactta catgatcatt tcgagagatg taatgttgat tgctgctgtt 720 ttttatgtca gataccgaac tcttccaaca ccacgaacac ttgccaagta tttcaatcct 780 tgctatgcca ctgctaggtt aaaaccaaca ttcatcagca aggtgaatac agcagtccag 840 ttaatcttgg tggcagcttc tttggcagct ccagttttca actatgctga cagcatttat 900 cttcagatac tatggtgttt tacagctttc accacagctg catcagctta tagttactat 960 cattatggcc ggaagactgt tcaggtgata aaagactgat gaaagtcatc cctcactgtt 1020 agtaaggaag cagtatacat caatgggaac agggcccatg gaaatgtaca ggagtttccc 1080 tattttggtg ttcagcttga aaaaggactt gtcagaatca actgtgtcat caaaatttaa 1140 gtaatgtgca ttgaaaataa ggttgatcat gggaatatgc agaatttcca atgtattttt 1200 aaatacaaat aaaattgtaa tttagaattt ttaaaaaaaa a 1241 112 301 PRT Homo Sapiens 112 Met Leu Ala Leu Arg Val Ala Arg Gly Ser Trp Gly Ala Leu Arg Gly 1 5 10 15 Ala Ala Trp Ala Pro Gly Thr Arg Pro Ser Lys Arg Arg Ala Cys Trp 20 25 30 Ala Leu Leu Pro Pro Val Pro Cys Cys Leu Gly Cys Leu Ala Glu Arg 35 40 45 Trp Arg Leu Arg Pro Ala Ala Leu Gly Leu Arg Leu Pro Gly Ile Gly 50 55 60 Gln Arg Asn His Cys Ser Gly Ala Gly Lys Ala Ala Pro Arg Pro Ala 65 70 75 80 Ala Gly Ala Gly Ala Ala Ala Glu Ala Pro Gly Gly Gln Trp Gly Pro 85 90 95 Ala Ser Thr Pro Ser Leu Tyr Glu Asn Pro Trp Thr Ile Pro Asn Met 100 105 110 Leu Ser Met Thr Arg Ile Gly Leu Ala Pro Val Leu Gly Tyr Leu Ile 115 120 125 Ile Glu Glu Asp Phe Asn Ile Ala Leu Gly Val Phe Ala Leu Ala Gly 130 135 140 Leu Thr Asp Leu Leu Asp Gly Phe Ile Ala Arg Asn Trp Ala Asn Gln 145 150 155 160 Arg Ser Ala Leu Gly Ser Ala Leu Asp Pro Leu Ala Asp Lys Ile Leu 165 170 175 Ile Ser Ile Leu Tyr Val Ser Leu Thr Tyr Ala Asp Leu Ile Pro Val 180 185 190 Pro Leu Thr Tyr Met Ile Ile Ser Arg Asp Val Met Leu Ile Ala Ala 195 200 205 Val Phe Tyr Val Arg Tyr Arg Thr Leu Pro Thr Pro Arg Thr Leu Ala 210 215 220 Lys Tyr Phe Asn Pro Cys Tyr Ala Thr Ala Arg Leu Lys Pro Thr Phe 225 230 235 240 Ile Ser Lys Val Asn Thr Ala Val Gln Leu Ile Leu Val Ala Ala Ser 245 250 255 Leu Ala Ala Pro Val Phe Asn Tyr Ala Asp Ser Ile Tyr Leu Gln Ile 260 265 270 Leu Trp Cys Phe Thr Ala Phe Thr Thr Ala Ala Ser Ala Tyr Ser Tyr 275 280 285 Tyr His Tyr Gly Arg Lys Thr Val Gln Val Ile Lys Asp 290 295 300 113 2906 DNA Homo Sapiens 113 gctccggccc gccccgctgc ccggcccgcg cgccgggcca tggagctgcg ggatgtgtcg 60 ctgcaggacc cgcgggaccg cttcgagctg ctgcagcgcg tgggggccgg gacctatggc 120 gacgtctaca aggcccgcga cacggtcacg tccgaactgg ccgccgtgaa gatagtcaag 180 ctagacccag gggacgacat cagctccctc cagcaggaaa tcaccatcct gcgtgagtgc 240 cgccacccca atgtggtggc ctacattggc agctacctca ggaatgaccg cttgtggatc 300 tgcatggagt tctgcggagg gggctccctg caggagattt accatgccac tgggcccctg 360 gaggagcggc agattgccta cgtctgccga gagcgactga aggggctcca ccacctgcat 420 tctcagggga agatccacag agacatcaag ggagccaacc ttctcctcac tctccaggga 480 gatgtcaaac tggctgactt tggggtgtca ggcgagctga cagcgtctgt ggccaagagg 540 aggtctttca ttgggactcc ctactggatg gctcccgagg tggctgctgt ggagcgcaaa 600 ggtggctaca atgagctatg tgacgtctgg gccctgggca tcactgccat tgagctgggc 660 gagctgcagc cccctctgtt ccacctgcac cccatgaggg ccctgatgct catgtcgaag 720 agcagcttcc agccgcccaa actgagagat aagactcgct ggacccagaa tttccaccac 780 tttctcaaac tggccctgac caagaatcct aagaagaggc cgacagcaga gaagctcctg 840 cagcacccgt tcacgactca gcagctccct cgggccctcc tcacacagct gctggacaaa 900 gccagtgacc ctcatctggg gaccccctcc cctgaggact gtgagctgga gacctatgac 960 atgtttccag acaccattca ctcccggggg cagcacggcc cagccgagag gaccccctcg 1020 gagatccagt ttcaccaggt gaaatttggc gccccacgca ggaaggaaac tgacccactg 1080 aatgagccgt gggaggaaga gtggacacta ctgggaaagg aagagttgag tgggagcctg 1140 ctgcagtcgg tccaggaggc cctggaggaa aggagtctga ctattcggtc agcctcagaa 1200 ttccaggagc tggactcccc agacgatacc atgggaacca tcaagcgggc cccgttccta 1260 gggccactcc ccactgaccc tccagcagag gagcctctgt ccagtccccc aggaaccctg 1320 cccccacctc cttcaggccc caacagctcc ccactgctgc ccacggcctg ggccaccatg 1380 aagcagcggg aggatcctga gaggtcatcc tgccacgggc tccccccaac tcccaaggtg 1440 catatgggcg cctgcttctc caaggtcttc aatggctgcc ccctgcggat ccacgctgct 1500 gtcacctgga ttcaccctgt tactcgggac cagttcctgg tggtaggggc cgaggaaggc 1560 atctacacac tcaacctgca tgaactgcat gaggatacgc tggagaagct gatttcacat 1620 cgctgctcct ggctctactg cgtgaacaac gtgctgctgt cactctcagg gaaatccacg 1680 cacatctggg cccatgacct cccaggcctg tttgagcagc ggaggctaca gcaacaggtt 1740 cccctctcca tccccaccaa ccgcctcacc cagcgcatca tccccaggcg ctttgctctg 1800 tccaccaaga ttcctgacac caaaggctgc ttgcagtgtc gtgtggtgcg gaacccctac 1860 acgggtgcca ccttcctgct ggccgccctg cccaccagcc tgctcctgct gcagtggtat 1920 gagccgctgc agaagtttct gctgctgaag aacttctcca gccctctgcc cagcccagct 1980 gggatgctgg agccgctggt gctggatggg aaggagctgc cgcaggtgtg tgttggggcc 2040 gaggggcctg aggggcccgg ctgccgcgtc ctgttccatg tcctgcccct ggaggctggc 2100 ctgacgcccg acatcctcat cccacctgag gggatcccag gctcggccca gcaggtgatc 2160 caggtggaca gggacacaat cctagtcagc tttgaacgct gtgtgaggat tgtcaacatg 2220 cagggcgagc ccacggccac actggcacct gagctgacct ttgatttccc catcgagact 2280 gtggtgtgcc tgcaggacag tgtgctggcc ttctggagcc atgggatgca aggccgaagc 2340 ctggatacca atgaggtgac ccaggagatc acagatgaaa caaggatctt ccgagtgctt 2400 ggggcccaca gagacatcat cctggagagc attcccactg acaacccaga ggcgcacagc 2460 aacctctaca tcctcacggg ccaccagagc acctactaag agcagcgggc ctgtccaggc 2520 tccccgcccc accccacgcc ttagctgcag gcccttttgg gcaaaggggc ccatcctaga 2580 ccagaggagc ccaggccctg gccctgctgg ggctgaaggt cagaagtaat cctgagaaat 2640 gtttcaggcc tggggaggga ggggagcccc cgacgcctct gcaataactg gaccaggggg 2700 agctgctgtc actcccccat ccccgaggca gcccagtccc tagtgcccaa ggcagggacc 2760 ctgggcctgg gccatccatt ccattttgtt ccacatttcc tttctactct ttctgccaag 2820 agcctgcccc tgcatttgtc ctgggaaaca cggtatttaa gagagaacta tattggtatt 2880 aaagctggtt tgttttaaaa aaaaaa 2906 114 765 PRT Homo Sapiens VARIANT (1)...(765) Xaa = Any Amino Acid 114 Trp Arg Arg Leu Gln Gly Pro Arg His Gly His Val Arg Thr Gly Arg 1 5 10 15 Arg Glu Asp Ser Gln Ala Arg Pro Arg Gly Arg His Gln Leu Pro Pro 20 25 30 Ala Gly Asn His His Pro Ala Val Pro Pro Pro Gln Cys Gly Gly Leu 35 40 45 His Trp Gln Leu Pro Gln Glu Pro Leu Val Asp Leu His Gly Val Leu 50 55 60 Arg Arg Gly Leu Pro Ala Gly Asp Leu Pro Cys His Trp Ala Pro Gly 65 70 75 80 Gly Ala Ala Asp Cys Leu Arg Leu Pro Arg Ala Thr Glu Gly Ala Pro 85 90 95 Pro Pro Ala Phe Ser Gly Glu Asp Pro Gln Arg His Gln Gly Ser Gln 100 105 110 Pro Ser Pro His Ser Pro Gly Arg Cys Gln Thr Gly Leu Trp Gly Val 115 120 125 Arg Arg Ala Asp Ser Val Cys Gly Gln Glu Glu Val Phe His Trp Asp 130 135 140 Ser Leu Leu Asp Gly Ser Arg Gly Gly Cys Cys Gly Ala Gln Arg Trp 145 150 155 160 Leu Gln Ala Met Arg Leu Gly Pro Gly His His Cys His Ala Gly Arg 165 170 175 Ala Ala Ala Pro Ser Val Pro Pro Ala Pro His Glu Gly Pro Asp Ala 180 185 190 His Val Glu Glu Gln Leu Pro Ala Ala Gln Thr Glu Arg Asp Ser Leu 195 200 205 Asp Pro Glu Phe Pro Pro Leu Ser Gln Thr Gly Pro Asp Gln Glu Ser 210 215 220 Glu Glu Ala Asp Ser Arg Glu Ala Pro Ala Ala Pro Val His Asp Ser 225 230 235 240 Ala Ala Pro Ser Gly Pro Pro His Thr Ala Ala Gly Gln Ser Gln Pro 245 250 255 Ser Ser Gly Asp Pro Leu Pro Gly Leu Ala Gly Asp Leu His Val Ser 260 265 270 Arg His His Ser Leu Pro Gly Ala Ala Arg Pro Ser Arg Glu Asp Pro 275 280 285 Leu Gly Asp Pro Val Ser Pro Gly Glu Ile Trp Arg Pro Thr Gln Glu 290 295 300 Gly Asn Pro Thr Glu Ala Val Gly Gly Arg Val Asp Thr Thr Gly Lys 305 310 315 320 Gly Arg Val Glu Trp Glu Pro Ala Ala Val Gly Pro Gly Gly Pro Gly 325 330 335 Gly Lys Glu Ser Asp Tyr Ser Val Ser Leu Arg Ile Pro Gly Ala Gly 340 345 350 Leu Pro Arg Arg Tyr His Gly Asn His Gln Ala Gly Pro Val Pro Arg 355 360 365 Ala Thr Pro His Pro Ser Ser Arg Gly Ala Ser Val Gln Ser Pro Arg 370 375 380 Asn Pro Ala Pro Thr Ser Phe Arg Pro Gln Gln Leu Pro Thr Ala Ala 385 390 395 400 His Gly Leu Gly His His Glu Ala Ala Gly Gly Ser Glu Val Ile Leu 405 410 415 Pro Arg Ala Pro Pro Asn Ser Gln Gly Ala Tyr Gly Arg Leu Leu Leu 420 425 430 Gln Gly Leu Gln Trp Leu Pro Pro Ala Asp Pro Arg Cys Cys His Leu 435 440 445 Asp Ser Pro Cys Tyr Ser Gly Pro Val Pro Gly Gly Arg Gly Arg Gly 450 455 460 Arg His Leu His Thr Gln Pro Ala Thr Ala Gly Tyr Ala Gly Glu Ala 465 470 475 480 Asp Phe Thr Ser Leu Leu Leu Ala Leu Leu Arg Glu Gln Arg Ala Ala 485 490 495 Val Thr Leu Arg Glu Ile His Ala His Leu Gly Pro Pro Pro Arg Pro 500 505 510 Val Ala Ala Glu Ala Thr Ala Thr Gly Ser Pro Leu His Pro His Gln 515 520 525 Pro Pro His Pro Ala His His Pro Gln Ala Leu Cys Ser Val His Gln 530 535 540 Asp Ser His Gln Arg Leu Leu Ala Val Ser Cys Gly Ala Glu Pro Leu 545 550 555 560 His Gly Cys His Leu Pro Ala Gly Arg Pro Ala His Gln Pro Ala Pro 565 570 575 Ala Ala Val Val Ala Ala Ala Glu Val Ser Ala Ala Glu Glu Leu Leu 580 585 590 Gln Pro Ser Ala Gln Pro Ser Trp Asp Ala Gly Ala Ala Gly Ala Gly 595 600 605 Trp Glu Gly Ala Ala Ala Gly Val Cys Trp Gly Arg Gly Ala Gly Ala 610 615 620 Arg Leu Pro Arg Pro Val Pro Cys Pro Ala Pro Gly Gly Trp Pro Asp 625 630 635 640 Ala Arg His Pro His Pro Thr Gly Asp Pro Arg Leu Gly Pro Ala Gly 645 650 655 Asp Pro Gly Gly Gln Gly His Asn Pro Ser Gln Leu Thr Leu Cys Glu 660 665 670 Asp Cys Gln His Ala Gly Arg Ala His Gly His Thr Gly Thr Ala Asp 675 680 685 Leu Phe Pro His Arg Asp Cys Gly Val Pro Ala Gly Gln Cys Ala Gly 690 695 700 Leu Leu Glu Pro Trp Asp Ala Arg Pro Lys Pro Gly Tyr Gln Gly Asp 705 710 715 720 Pro Gly Asp His Arg Asn Lys Asp Leu Pro Ser Ala Trp Gly Pro Gln 725 730 735 Arg His His Pro Gly Glu His Ser His Gln Pro Arg Gly Ala Gln Gln 740 745 750 Pro Leu His Pro His Gly Pro Pro Glu His Leu Leu Xaa 755 760 765 115 3335 DNA Homo Sapiens misc_feature (1)...(3335) n = A,T,C or G 115 ggcatcactc gagcccaggt cccagtcatc accactcaca gcgctcggcg ttcaggaaga 60 ggagcaccag cggagcgcgg ctgcttcagc ggcgggcggg cgccagaaag gccccgatcg 120 aaaagcctgg gagggccgcc gaactacccc cggagggagg agccagtccg aacccaaggc 180 gccaccgccg cagaagcgga gcgaggcagc attcgcctcc atggcccact cgccggtggc 240 tgtccaagtg cctgggatgc agaataacat agctgatcca gaagaactgt tcacaaaatt 300 agagcgcatt gggaaaggct catttgggga agttttcaaa ggaattgata accgtaccca 360 gcaagtcgtt gctattaaaa tcatagacct tgaggaagcc gaagatgaaa tagaagacat 420 tcagcaagaa ataactgtct tgagtcaatg tgacagctca tatgtaacaa aatactatgg 480 gtcatattta aaggggtcta aattatggat aataatggaa tacctgggcg gtggttcagc 540 actggatctt cttcgagctg gtccatttga tgagttccag attgctacca tgctaaagga 600 aattttaaaa ggtctggact atctgcattc agaaaagaaa attcaccgag acataaaagc 660 tgccaatgtc ttgctctcag aacaaggaga tgttaaactt gctgattttg gagttgctgg 720 tcagctgaca gatacacaga ttaaaagaaa tacctttgtg ggaactccat tttggatggc 780 tcctgaagtt attcaacagt cagcttatga ctcaaaagct gacatttggt cattgggaat 840 tactgctatt gaactagcca agggagagcc acctaactcc gatatgcatc caatgagagt 900 tctgtttctt attcccaaaa acaatcctcc aactcttgtt ggagacttta ctaagtcttt 960 taaggagttt attgatgctt gcctgaacaa agatccatca tttcgtccta cagcaaaaga 1020 acttctgaaa cacaaattca ttgtaaaaaa ttcaaagaag acttcttatc tgactgaact 1080 gatagatcgt tttaagagat ggaaggcaga aggacacagt gatgatgaat ctgattccga 1140 gggctctgat tcggaatcta ccagcaggga aaacaatact catcctgaat ggagctttac 1200 caccgtacga aagaagcctg atccaaagaa agtacagaat ggggcagagc aagatcttgt 1260 gcaaaccctg agttgtttgt ctatgataat cacacctgca tttgctgaac ttaaacagca 1320 ggacgagaat aacgctagca ggaatcaggc gattgaagaa ctcgagaaaa gtattgctgt 1380 ggctgaagcc gcctgtcccg gcatcacaga taaaatggtg aagaaactaa ttgaaaaatt 1440 tcaaaagtgt tcagcagacg aatcccccta agaaacttat tattggcttc tgtttcatat 1500 ggacccagag agccccacca aacctacgtc aagattaaca atgcttaacc catgagctcc 1560 atgtgccttt tggatctttg caacactgaa gatttggaag aagctattaa actattttgt 1620 gatggcgttt atcattttat attttgaaag gattattttg taaggaataa cttttaatac 1680 tatagtttca cctgtattct agtaaatgtt gagacaccgt tttgctttta agtatcccta 1740 tttcttaagt tacgaggatg aatacctttc acattttgat ctttagttga ctctacagtc 1800 atgaaacata caggtctttc aaagtcattc tcaatattca gcttttgtaa attatcaagc 1860 ttcaaaaagc ttttttttta aaaaaaaaaa catgcatatt ctaaaaatng actattnngg 1920 tggggaggtn gtaaataagt cataccttct taaaacagaa aatttaagta aagtctttta 1980 aatgaaacct gtaaaagtat tgactcttct accaagttng gtnatgatat tccanggnca 2040 gctcaatgat tnatcacatt tgagaccctg tgtttganag catttacagg caatgtacag 2100 caacagaggn ntacctnctt ggtgtantag tatttacatt ctctntttna ggtagaagag 2160 gcaattttac ccnttatttc acatggttag aaatttaaag canagatcat ttacccaagg 2220 ataggtgttt ggtaatgttg aaggagtnta gtctggctnt cnantgtttt acatcttnca 2280 actaaaatcc catacntatc tgcttggatt tggagagcca aaaaataaag ctgattgtca 2340 tgtgattana atatctgatc aacaggntat gaatataact ntaaatcang catatttttg 2400 ccatggtaan ntaaatntgt cctantaaac tatntnntat atatttttgt tcttcataat 2460 tatcactaat aagcatcagt ttgttgtttt taaaaggata tttaagntga ngcattnttc 2520 tagttcatna ntgaaaataa ccatagtaca ggatgatttc tgtccacaca aaggttaaat 2580 tagatntgca cagttaattt tcacttatat ttatggtact attatgtggn gtgatgcctt 2640 ntttctttta agcccagtac atatattatg cctgcctaag ttctgaactn ggggctgtat 2700 ttcagtagnt ntgtagaatt attgatattt agttttgata gctaatgntt tananttgnt 2760 ttggatctgc acagtttggt ttttgcacaa aagtcattta aanaaaatct gagtaattgt 2820 caaatattaa aagaaagata ttcttcctgt aaggaataca gtttttagtc aaagtggcca 2880 ttacatnncc tctttttaan tttacataat acagatactt gagaaagttg ttgtggtgtt 2940 gtatgccaag aaaattnnct ttttnattgg tgcctatatt gtaacaatta tttttaatgc 3000 attgtatttt gaagtaacgg ttcagttaaa tttttcacct gnctgtgtaa ctgaagcaca 3060 attancagtt tatanatnca tctgtagaan gtctggnagn ataattttgc aactcatgtt 3120 atgggnttaa atgaatatnt tttgtaaaag taaaagcaac aanatttant aaattgatnn 3180 tatttganaa ctttacaaca cnaattgcat cccaaataca aattgtattg cttattcatt 3240 atagctattc gtcctgtaat ctgtttctag gtgaagcata ctccagtgtt ttaggggttt 3300 tgaaaataaa tatttaaatt tcacagtcaa aaaaa 3335 116 416 PRT Homo Sapiens 116 Met Ala His Ser Pro Val Ala Val Gln Val Pro Gly Met Gln Asn Asn 1 5 10 15 Ile Ala Asp Pro Glu Glu Leu Phe Thr Lys Leu Glu Arg Ile Gly Lys 20 25 30 Gly Ser Phe Gly Glu Val Phe Lys Gly Ile Asp Asn Arg Thr Gln Gln 35 40 45 Val Val Ala Ile Lys Ile Ile Asp Leu Glu Glu Ala Glu Asp Glu Ile 50 55 60 Glu Asp Ile Gln Gln Glu Ile Thr Val Leu Ser Gln Cys Asp Ser Ser 65 70 75 80 Tyr Val Thr Lys Tyr Tyr Gly Ser Tyr Leu Lys Gly Ser Lys Leu Trp 85 90 95 Ile Ile Met Glu Tyr Leu Gly Gly Gly Ser Ala Leu Asp Leu Leu Arg 100 105 110 Ala Gly Pro Phe Asp Glu Phe Gln Ile Ala Thr Met Leu Lys Glu Ile 115 120 125 Leu Lys Gly Leu Asp Tyr Leu His Ser Glu Lys Lys Ile His Arg Asp 130 135 140 Ile Lys Ala Ala Asn Val Leu Leu Ser Glu Gln Gly Asp Val Lys Leu 145 150 155 160 Ala Asp Phe Gly Val Ala Gly Gln Leu Thr Asp Thr Gln Ile Lys Arg 165 170 175 Asn Thr Phe Val Gly Thr Pro Phe Trp Met Ala Pro Glu Val Ile Gln 180 185 190 Gln Ser Ala Tyr Asp Ser Lys Ala Asp Ile Trp Ser Leu Gly Ile Thr 195 200 205 Ala Ile Glu Leu Ala Lys Gly Glu Pro Pro Asn Ser Asp Met His Pro 210 215 220 Met Arg Val Leu Phe Leu Ile Pro Lys Asn Asn Pro Pro Thr Leu Val 225 230 235 240 Gly Asp Phe Thr Lys Ser Phe Lys Glu Phe Ile Asp Ala Cys Leu Asn 245 250 255 Lys Asp Pro Ser Phe Arg Pro Thr Ala Lys Glu Leu Leu Lys His Lys 260 265 270 Phe Ile Val Lys Asn Ser Lys Lys Thr Ser Tyr Leu Thr Glu Leu Ile 275 280 285 Asp Arg Phe Lys Arg Trp Lys Ala Glu Gly His Ser Asp Asp Glu Ser 290 295 300 Asp Ser Glu Gly Ser Asp Ser Glu Ser Thr Ser Arg Glu Asn Asn Thr 305 310 315 320 His Pro Glu Trp Ser Phe Thr Thr Val Arg Lys Lys Pro Asp Pro Lys 325 330 335 Lys Val Gln Asn Gly Ala Glu Gln Asp Leu Val Gln Thr Leu Ser Cys 340 345 350 Leu Ser Met Ile Ile Thr Pro Ala Phe Ala Glu Leu Lys Gln Gln Asp 355 360 365 Glu Asn Asn Ala Ser Arg Asn Gln Ala Ile Glu Glu Leu Glu Lys Ser 370 375 380 Ile Ala Val Ala Glu Ala Ala Cys Pro Gly Ile Thr Asp Lys Met Val 385 390 395 400 Lys Lys Leu Ile Glu Lys Phe Gln Lys Cys Ser Ala Asp Glu Ser Pro 405 410 415 117 1800 DNA Homo Sapiens 117 actgcgaccc ggagccgccc ggactgacgg agcccactgc ggtgcgggcg ttggcgcggg 60 cacggaggac ccgggcaggc atcgcaagcg accccgagcg gagccccgga gccatggccc 120 tgagcgagct ggcgctggtc cgctggctgc aggagagccg ccgctcgcgg aagctcatcc 180 tgttcatcgt gttcctggcg ctgctgctgg acaacatgct gctcactgtc gtggtcccca 240 tcatcccaag ttatctgtac agcattaagc atgagaagaa tgctacagaa atccagacgg 300 ccaggccagt gcacactgcc tccatctcag acagcttcca gagcatcttc tcctattatg 360 ataactcgac tatggtcacc gggaatgcta ccagagacct gacacttcat cagaccgcca 420 cacagcacat ggtgaccaac gcgtccgctg ttccttccga ctgtcccagt gaagacaaag 480 acctcctgaa tgaaaacgtg caagttggtc tgttgtttgc ctcgaaagcc accgtccagc 540 tcatcaccaa ccctttcata ggactactga ccaacagaat tggctatcca attcccatat 600 ttgcgggatt ctgcatcatg tttgtctcaa caattatgtt tgccttctcc agcagctatg 660 ccttcctgct gattgccagg tcgctgcagg gcatcggctc gtcctgctcc tctgtggctg 720 ggatgggcat gcttgccagt gtctacacag atgatgaaga gagaggcaac gtcatgggaa 780 tcgccttggg aggcctggcc atgggggtct tagtgggccc ccccttcggg agtgtgctct 840 atgagtttgt ggggaagacg gctccgttcc tggtgctggc cgccctggta ctcttggatg 900 gagctattca gctctttgtg ctccagccgt cccgggtgca gccagagagt cagaagggga 960 cacccctaac cacgctgctg aaggacccgt acatcctcat tgctgcaggc tccatctgct 1020 ttgcaaacat gggcatcgcc atgctggagc cagccctgcc catctggatg atggagacca 1080 tgtgttcccg aaagtggcag ctgggcgttg ccttcttgcc agctagtatc tcttatctca 1140 ttggaaccaa tatttttggg atacttgcac acaaaatggg gaggtggctt tgtgctcttc 1200 tgggaatgat aattgttgga gtcagcattt tatgtattcc atttgcaaaa aacatttatg 1260 gactcatagc tccgaacttt ggagttggtt ttgcaattgg aatggtggat tcgtcaatga 1320 tgcctatcat gggctacctc gtagacctgc ggcacgtgtc cgtctatggg agtgtgtacg 1380 ccattgcgga tgtggcattt tgtatggggt atgctatagg tccttctgct ggtggtgcta 1440 ttgcaaaggc aattggattt ccatggctca tgacaattat tgggataatt gatattcttt 1500 ttgcccctct ctgctttttt cttcgaagtc cacctgccaa agaagaaaaa atggctattc 1560 tcatggatca caactgccct attaaaacaa aaatgtacac tcagaataat atccagtcat 1620 atccgatagg tgaagatgaa gaatctgaaa gtgactgaga tgagatcctc aaaaatcatc 1680 aaagtgttta attgtataaa acagtgtttc cagtgacaca actcatccag aactgtctta 1740 gtcataccat ccatccctgg tgaaagagta aaaccaaagg ttattatttc ctttccatgg 1800 118 514 PRT Homo Sapiens 118 Met Ala Leu Ser Glu Leu Ala Leu Val Arg Trp Leu Gln Glu Ser Arg 1 5 10 15 Arg Ser Arg Lys Leu Ile Leu Phe Ile Val Phe Leu Ala Leu Leu Leu 20 25 30 Asp Asn Met Leu Leu Thr Val Val Val Pro Ile Ile Pro Ser Tyr Leu 35 40 45 Tyr Ser Ile Lys His Glu Lys Asn Ala Thr Glu Ile Gln Thr Ala Arg 50 55 60 Pro Val His Thr Ala Ser Ile Ser Asp Ser Phe Gln Ser Ile Phe Ser 65 70 75 80 Tyr Tyr Asp Asn Ser Thr Met Val Thr Gly Asn Ala Thr Arg Asp Leu 85 90 95 Thr Leu His Gln Thr Ala Thr Gln His Met Val Thr Asn Ala Ser Ala 100 105 110 Val Pro Ser Asp Cys Pro Ser Glu Asp Lys Asp Leu Leu Asn Glu Asn 115 120 125 Val Gln Val Gly Leu Leu Phe Ala Ser Lys Ala Thr Val Gln Leu Ile 130 135 140 Thr Asn Pro Phe Ile Gly Leu Leu Thr Asn Arg Ile Gly Tyr Pro Ile 145 150 155 160 Pro Ile Phe Ala Gly Phe Cys Ile Met Phe Val Ser Thr Ile Met Phe 165 170 175 Ala Phe Ser Ser Ser Tyr Ala Phe Leu Leu Ile Ala Arg Ser Leu Gln 180 185 190 Gly Ile Gly Ser Ser Cys Ser Ser Val Ala Gly Met Gly Met Leu Ala 195 200 205 Ser Val Tyr Thr Asp Asp Glu Glu Arg Gly Asn Val Met Gly Ile Ala 210 215 220 Leu Gly Gly Leu Ala Met Gly Val Leu Val Gly Pro Pro Phe Gly Ser 225 230 235 240 Val Leu Tyr Glu Phe Val Gly Lys Thr Ala Pro Phe Leu Val Leu Ala 245 250 255 Ala Leu Val Leu Leu Asp Gly Ala Ile Gln Leu Phe Val Leu Gln Pro 260 265 270 Ser Arg Val Gln Pro Glu Ser Gln Lys Gly Thr Pro Leu Thr Thr Leu 275 280 285 Leu Lys Asp Pro Tyr Ile Leu Ile Ala Ala Gly Ser Ile Cys Phe Ala 290 295 300 Asn Met Gly Ile Ala Met Leu Glu Pro Ala Leu Pro Ile Trp Met Met 305 310 315 320 Glu Thr Met Cys Ser Arg Lys Trp Gln Leu Gly Val Ala Phe Leu Pro 325 330 335 Ala Ser Ile Ser Tyr Leu Ile Gly Thr Asn Ile Phe Gly Ile Leu Ala 340 345 350 His Lys Met Gly Arg Trp Leu Cys Ala Leu Leu Gly Met Ile Ile Val 355 360 365 Gly Val Ser Ile Leu Cys Ile Pro Phe Ala Lys Asn Ile Tyr Gly Leu 370 375 380 Ile Ala Pro Asn Phe Gly Val Gly Phe Ala Ile Gly Met Val Asp Ser 385 390 395 400 Ser Met Met Pro Ile Met Gly Tyr Leu Val Asp Leu Arg His Val Ser 405 410 415 Val Tyr Gly Ser Val Tyr Ala Ile Ala Asp Val Ala Phe Cys Met Gly 420 425 430 Tyr Ala Ile Gly Pro Ser Ala Gly Gly Ala Ile Ala Lys Ala Ile Gly 435 440 445 Phe Pro Trp Leu Met Thr Ile Ile Gly Ile Ile Asp Ile Leu Phe Ala 450 455 460 Pro Leu Cys Phe Phe Leu Arg Ser Pro Pro Ala Lys Glu Glu Lys Met 465 470 475 480 Ala Ile Leu Met Asp His Asn Cys Pro Ile Lys Thr Lys Met Tyr Thr 485 490 495 Gln Asn Asn Ile Gln Ser Tyr Pro Ile Gly Glu Asp Glu Glu Ser Glu 500 505 510 Ser Asp 119 2157 DNA Homo Sapiens 119 cgatcctgcc ggagccccgc cgccgccggc ttggattctg aaaccttcct tgtatccctc 60 ctgagacatc tttgctgcaa gatcgaggct gtcctctggt gagaaggtgg tgaggcttcc 120 cgtcatattc cagctctgaa cagcaacatg gggtgcaaag tcctgctcaa cattgggcag 180 cagatgctgc ggcggaaggt ggtggactgt agccgggagg agacgcggct gtctcgctgc 240 ctgaacactt ttgatctggt ggccctcggg gtgggcagca cactgggtgc tggtgtctac 300 gtcctggctg gagctgtggc ccgtgagaat gcaggccctg ccattgtcat ctccttcctg 360 atcgctgcgc tggcctcagt gctggctggc ctgtgctatg gcgagtttgg tgctcgggtc 420 cccaagacgg gctcagctta cctctacagc tatgtcaccg ttggagagct ctgggccttc 480 atcaccggct ggaacttaat cctctcctac atcatcggta cttcaagcgt agcgagggcc 540 tggagcgcca ccttcgacga gctgataggc agacccatcg gggagttctc acggacacac 600 atgactctga acgcccccgg cgtgctggct gaaaaccccg acatattcgc agtgatcata 660 attctcatct tgacaggact tttaactctt ggtgtgaaag agtcggccat ggtcaacaaa 720 atattcactt gtattaacgt cctggtcctg ggcttcataa tggtgtcagg atttgtgaaa 780 ggatcggtta aaaactggca gctcacggag gaggattttg ggaacacatc aggccgtctc 840 tgtttgaaca atgacacaaa agaagggaag cccggtgttg gtggattcat gcccttcggg 900 ttctctggtg tcctgtcggg ggcagcgact tgcttctatg ccttcgtggg ctttgactgc 960 atcgccacca caggtgaaga ggtgaagaac ccacagaagg ccatccccgt ggggatcgtg 1020 gcgtccctct tgatctgctt catcgcctac tttggggtgt cggctgccct cacgctcatg 1080 atgccctact tctgcctgga caataacagc cccctgcccg acgcctttaa gcacgtgggc 1140 tgggaaggtg ccaagtacgc agtggccgtg ggctccctct gcgctctttc cgccagtctt 1200 ctaggttcca tgtttcccat gcctcgggtt atctatgcca tggctgagga tggactgcta 1260 tttaaattct tagccaacgt caatgatagg accaaaacac caataatcgc cacattagcc 1320 tcgggtgccg ttgctgctgt gatggccttc ctctttgacc tgaaggactt ggtggacctc 1380 atgtccattg gcactctcct ggcttactcg ttggtggctg cctgtgtgtt ggtcttacgg 1440 taccagccag agcagcctaa cctggtatac cagatggcca gtacttccga cgagttagat 1500 ccagcagacc aaaatgaatt ggcaagcacc aatgattccc agctggggtt tttaccagag 1560 gcagagatgt tctctttgaa aaccatactc tcacccaaaa acatggagcc ttccaaaatc 1620 tctgggctaa ttgtgaacat ttcaaccagc cttatagctg ttctcatcat caccttctgc 1680 attgtgaccg tgcttggaag ggaggctctc accaaagggg cgctgtgggc agtctttctg 1740 ctcgcagggt ctgccctcct ctgtgccgtg gtcacgggcg tcatctggag gcagcccgag 1800 agcaagacca agctctcatt taaggttccc ttcctgccag tgctccccat cctgagcatc 1860 ttcgtgaacg tctatctcat gatgcagctg gaccagggca cctgggtccg gtttgctgtg 1920 tggatgctga taggcttcat catctacttt ggctatggcc tgtggcacag cgaggaggcg 1980 tccctggatg ccgaccaagc aaggactcct gacggcaact tggaccagtg caagtgacgc 2040 acagccccgc cccccggagg tggcagcagc cccgagggac gcccccagag gaccgggagg 2100 caccccaccc tccccaccag tgcaacagaa accacctgcg tccacaccct cactgca 2157 120 629 PRT Homo Sapiens 120 Met Gly Cys Lys Val Leu Leu Asn Ile Gly Gln Gln Met Leu Arg Arg 1 5 10 15 Lys Val Val Asp Cys Ser Arg Glu Glu Thr Arg Leu Ser Arg Cys Leu 20 25 30 Asn Thr Phe Asp Leu Val Ala Leu Gly Val Gly Ser Thr Leu Gly Ala 35 40 45 Gly Val Tyr Val Leu Ala Gly Ala Val Ala Arg Glu Asn Ala Gly Pro 50 55 60 Ala Ile Val Ile Ser Phe Leu Ile Ala Ala Leu Ala Ser Val Leu Ala 65 70 75 80 Gly Leu Cys Tyr Gly Glu Phe Gly Ala Arg Val Pro Lys Thr Gly Ser 85 90 95 Ala Tyr Leu Tyr Ser Tyr Val Thr Val Gly Glu Leu Trp Ala Phe Ile 100 105 110 Thr Gly Trp Asn Leu Ile Leu Ser Tyr Ile Ile Gly Thr Ser Ser Val 115 120 125 Ala Arg Ala Trp Ser Ala Thr Phe Asp Glu Leu Ile Gly Arg Pro Ile 130 135 140 Gly Glu Phe Ser Arg Thr His Met Thr Leu Asn Ala Pro Gly Val Leu 145 150 155 160 Ala Glu Asn Pro Asp Ile Phe Ala Val Ile Ile Ile Leu Ile Leu Thr 165 170 175 Gly Leu Leu Thr Leu Gly Val Lys Glu Ser Ala Met Val Asn Lys Ile 180 185 190 Phe Thr Cys Ile Asn Val Leu Val Leu Gly Phe Ile Met Val Ser Gly 195 200 205 Phe Val Lys Gly Ser Val Lys Asn Trp Gln Leu Thr Glu Glu Asp Phe 210 215 220 Gly Asn Thr Ser Gly Arg Leu Cys Leu Asn Asn Asp Thr Lys Glu Gly 225 230 235 240 Lys Pro Gly Val Gly Gly Phe Met Pro Phe Gly Phe Ser Gly Val Leu 245 250 255 Ser Gly Ala Ala Thr Cys Phe Tyr Ala Phe Val Gly Phe Asp Cys Ile 260 265 270 Ala Thr Thr Gly Glu Glu Val Lys Asn Pro Gln Lys Ala Ile Pro Val 275 280 285 Gly Ile Val Ala Ser Leu Leu Ile Cys Phe Ile Ala Tyr Phe Gly Val 290 295 300 Ser Ala Ala Leu Thr Leu Met Met Pro Tyr Phe Cys Leu Asp Asn Asn 305 310 315 320 Ser Pro Leu Pro Asp Ala Phe Lys His Val Gly Trp Glu Gly Ala Lys 325 330 335 Tyr Ala Val Ala Val Gly Ser Leu Cys Ala Leu Ser Ala Ser Leu Leu 340 345 350 Gly Ser Met Phe Pro Met Pro Arg Val Ile Tyr Ala Met Ala Glu Asp 355 360 365 Gly Leu Leu Phe Lys Phe Leu Ala Asn Val Asn Asp Arg Thr Lys Thr 370 375 380 Pro Ile Ile Ala Thr Leu Ala Ser Gly Ala Val Ala Ala Val Met Ala 385 390 395 400 Phe Leu Phe Asp Leu Lys Asp Leu Val Asp Leu Met Ser Ile Gly Thr 405 410 415 Leu Leu Ala Tyr Ser Leu Val Ala Ala Cys Val Leu Val Leu Arg Tyr 420 425 430 Gln Pro Glu Gln Pro Asn Leu Val Tyr Gln Met Ala Ser Thr Ser Asp 435 440 445 Glu Leu Asp Pro Ala Asp Gln Asn Glu Leu Ala Ser Thr Asn Asp Ser 450 455 460 Gln Leu Gly Phe Leu Pro Glu Ala Glu Met Phe Ser Leu Lys Thr Ile 465 470 475 480 Leu Ser Pro Lys Asn Met Glu Pro Ser Lys Ile Ser Gly Leu Ile Val 485 490 495 Asn Ile Ser Thr Ser Leu Ile Ala Val Leu Ile Ile Thr Phe Cys Ile 500 505 510 Val Thr Val Leu Gly Arg Glu Ala Leu Thr Lys Gly Ala Leu Trp Ala 515 520 525 Val Phe Leu Leu Ala Gly Ser Ala Leu Leu Cys Ala Val Val Thr Gly 530 535 540 Val Ile Trp Arg Gln Pro Glu Ser Lys Thr Lys Leu Ser Phe Lys Val 545 550 555 560 Pro Phe Leu Pro Val Leu Pro Ile Leu Ser Ile Phe Val Asn Val Tyr 565 570 575 Leu Met Met Gln Leu Asp Gln Gly Thr Trp Val Arg Phe Ala Val Trp 580 585 590 Met Leu Ile Gly Phe Ile Ile Tyr Phe Gly Tyr Gly Leu Trp His Ser 595 600 605 Glu Glu Ala Ser Leu Asp Ala Asp Gln Ala Arg Thr Pro Asp Gly Asn 610 615 620 Leu Asp Gln Cys Lys 625 121 3807 DNA Homo Sapiens 121 atggcgagcg actccccggc tcgaagcctg gatgaaatag atctctcggc tctgagggac 60 cctgcaggga tctttgaatt ggtggaactt gttggaaatg gaacatacgg gcaagtttat 120 aagggtcgtc atgtcaaaac gggccagctt gcagccatca aggttatgga tgtcacaggg 180 gatgaagagg aagaaatcaa acaagaaatt aacatgttga agaaatattc tcatcaccgg 240 aatattgcta catactatgg tgcttttatc aaaaagaacc caccaggcat ggatgaccaa 300 ctttggttgg tgatggagtt ttgtggtgct ggctctgtca ccgacctgat caagaacaca 360 aaaggtaaca cgttgaaaga ggagtggatt gcatacatct gcagggaaat cttacggggg 420 ctgagtcacc tgcaccagca taaagtgatt catcgagata ttaaagggca aaatgtcttg 480 ctgactgaaa atgcagaagt taaactagtg gactttggag tcagtgctca gcttgatcga 540 acagtgggca ggaggaatac tttcattgga actccctact ggatggcacc agaagttatt 600 gcctgtgatg aaaacccaga tgccacatat gatttcaaga gtgacttgtg gtctttgggt 660 atcaccgcca ttgaaatggc agaaggtgct ccccctctct gtgacatgca ccccatgaga 720 gctctcttcc tcatcccccg gaatccagcg cctcggctga agtctaagaa gtggtcaaaa 780 aaattccagt catttattga gagctgcttg gtaaagaatc acagccagcg accagcaaca 840 gaacaattga tgaagcatcc atttatacga gaccaaccta atgagcgaca ggtccgcatt 900 caactcaagg accatattga tagaacaaag aagaagcgag gagaaaaaga tgagacagag 960 tatgagtaca gtggaagtga ggaagaagag gaggagaatg actcaggaga gcccagctcc 1020 atcctgaatc tgccagggga gtcgacgctg cggagggact ttctgaggct gcagctggcc 1080 aacaaggagc gttctgaggc cctacggagg cagcagctgg agcagcagca gcgggagaat 1140 gaggagcaca agcggcagct gctggccgag cgtcagaagc gcatcgagga gcagaaagag 1200 cagaggcggc ggctggagga gcaacaaagg cgagagaagg agctgcggaa gcagcaggag 1260 agggagcagc gccggcacta tgaggagcag atgcgccggg aggaggagag gaggcgtgcg 1320 gagcatgaac aggaatataa gcgcaaacaa ttggaagaac agagacaagc agaaagactg 1380 cagaggcagc taaagcaaga aagagactac ttagtttccc ttcagcatca gcggcaggag 1440 cagaggcctg tggagaagaa gccactgtac cattacaaag aaggaatgag tcctagtgag 1500 aagccagcat gggccaagga gatcccacat ctggtagctg taaaatccca gggacctgcc 1560 ttgaccgcct cccagtcagt gcacgagcag cccacaaagg gcctctctgg gtttcaggag 1620 gctctgaacg tgacctccca ccgcgtggag atgccacgcc agaactcaga tcccacctcg 1680 gaaaatcctc ctctccccac tcgcattgaa aagtttgacc gaagctcttg gttacgacag 1740 gaagaagaca ttccaccaaa ggtgcctcaa agaacaactt ctatatcccc agcattagcc 1800 agaaagaatt ctcctgggaa tggtagtgct ctgggaccca gactaggatc tcaacccatc 1860 agagcaagca accctgatct ccggagaact gagcccatct tggagagccc cttgcagagg 1920 accagcagtg gcagttcctc cagctccagc acccctagct cccagcccag ctcccaagga 1980 ggctcccagc ctggatcaca agcaggatcc agtgaacgca ccagagttcg agccaacagt 2040 aagtcagaag gatcacctgt gcttccccat gagcctgcca aggtgaaacc agaagaatcc 2100 agggacatta cccggcccag tcgaccagct gatctgacgg cattagccaa agaactaaga 2160 gaactccgga ttgaagaaac aaaccgccca atgaagaagg tgactgatta ctcctcctcc 2220 agtgaggagt cagaaagtag cgaggaagag gaggaagatg gagagagcga gacccatgat 2280 gggacagtgg ctgtcagcga catacccaga ctgataccaa caggagctcc aggcagcaac 2340 gagcagtaca atgtgggaat ggtggggacg catgggctgg agacctctca tgcggacagt 2400 ttcagcggca gtatttcaag agaaggaacc ttgatgatta gagagacgtc tggagagaag 2460 aagcgatctg gccacagtga cagcaatggc tttgctggcc acatcaacct ccctgacctg 2520 gtgcagcaga gccattctcc agctggaacc ccgactgagg gactggggcg cgtctcaacc 2580 cattcccagg agatggactc tgggactgaa tatggcatgg ggagcagcac caaagcctcc 2640 ttcaccccct ttgtggaccc cagagtatac cagacgtctc ccactgatga agatgaagag 2700 gatgaggaat catcagccgc agctctgttt actagcgaac ttcttaggca agaacaggcc 2760 aaactcaatg aagcaagaaa gatttcggtg gtaaatgtaa acccaaccaa cattcggcct 2820 catagcgaca caccagaaat cagaaaatac aagaaacgat tcaactcaga aatactttgt 2880 gcagctctgt ggggtgtaaa ccttctggtg gggactgaaa atggcctgat gcttttggac 2940 cgaagtgggc aaggcaaagt ctataatctg atcaaccgga ggcgatttca gcagatggat 3000 gtgctagagg gactgaatgt ccttgtgaca atttcaggaa agaagaataa gctacgagtt 3060 tactatcttt catggttaag aaacagaata ctacataatg acccagaagt agaaaagaaa 3120 caaggctgga tcactgttgg ggacttggaa ggctgtatac attataaagt tgttaaatat 3180 gaaaggatca aatttttggt gattgcctta aagaatgctg tggaaatata tgcttgggct 3240 cctaaaccgt atcataaatt catggcattt aagtcttttg cagatctcca gcacaagcct 3300 ctgctagttg atctcacggt agaagaaggt caaagattaa aggttatttt tggttcacac 3360 actggtttcc atgtaattga tgttgattca ggaaactctt atgatatcta cataccatct 3420 catattcagg gcaatatcac tcctcatgct attgtcatct tgcctaaaac agatggaatg 3480 gaaatgcttg tttgctatga ggatgagggg gtgtatgtaa acacctatgg ccggataact 3540 aaggatgtgg tgctccaatg gggagaaatg cccacgtctg tggcctacat tcattccaat 3600 cagataatgg gctggggcga gaaagctatt gagatccggt cagtggaaac aggacatttg 3660 gatggagtat ttatgcataa gcgagctcaa aggttaaagt ttctatgtga aagaaatgat 3720 aaggtatttt ttgcatccgt gcgatctgga ggaagtagcc aagtgttttt catgaccctc 3780 aacagaaatt ccatgatgaa ctggtaa 3807 122 1268 PRT Homo Sapiens 122 Met Ala Ser Asp Ser Pro Ala Arg Ser Leu Asp Glu Ile Asp Leu Ser 1 5 10 15 Ala Leu Arg Asp Pro Ala Gly Ile Phe Glu Leu Val Glu Leu Val Gly 20 25 30 Asn Gly Thr Tyr Gly Gln Val Tyr Lys Gly Arg His Val Lys Thr Gly 35 40 45 Gln Leu Ala Ala Ile Lys Val Met Asp Val Thr Gly Asp Glu Glu Glu 50 55 60 Glu Ile Lys Gln Glu Ile Asn Met Leu Lys Lys Tyr Ser His His Arg 65 70 75 80 Asn Ile Ala Thr Tyr Tyr Gly Ala Phe Ile Lys Lys Asn Pro Pro Gly 85 90 95 Met Asp Asp Gln Leu Trp Leu Val Met Glu Phe Cys Gly Ala Gly Ser 100 105 110 Val Thr Asp Leu Ile Lys Asn Thr Lys Gly Asn Thr Leu Lys Glu Glu 115 120 125 Trp Ile Ala Tyr Ile Cys Arg Glu Ile Leu Arg Gly Leu Ser His Leu 130 135 140 His Gln His Lys Val Ile His Arg Asp Ile Lys Gly Gln Asn Val Leu 145 150 155 160 Leu Thr Glu Asn Ala Glu Val Lys Leu Val Asp Phe Gly Val Ser Ala 165 170 175 Gln Leu Asp Arg Thr Val Gly Arg Arg Asn Thr Phe Ile Gly Thr Pro 180 185 190 Tyr Trp Met Ala Pro Glu Val Ile Ala Cys Asp Glu Asn Pro Asp Ala 195 200 205 Thr Tyr Asp Phe Lys Ser Asp Leu Trp Ser Leu Gly Ile Thr Ala Ile 210 215 220 Glu Met Ala Glu Gly Ala Pro Pro Leu Cys Asp Met His Pro Met Arg 225 230 235 240 Ala Leu Phe Leu Ile Pro Arg Asn Pro Ala Pro Arg Leu Lys Ser Lys 245 250 255 Lys Trp Ser Lys Lys Phe Gln Ser Phe Ile Glu Ser Cys Leu Val Lys 260 265 270 Asn His Ser Gln Arg Pro Ala Thr Glu Gln Leu Met Lys His Pro Phe 275 280 285 Ile Arg Asp Gln Pro Asn Glu Arg Gln Val Arg Ile Gln Leu Lys Asp 290 295 300 His Ile Asp Arg Thr Lys Lys Lys Arg Gly Glu Lys Asp Glu Thr Glu 305 310 315 320 Tyr Glu Tyr Ser Gly Ser Glu Glu Glu Glu Glu Glu Asn Asp Ser Gly 325 330 335 Glu Pro Ser Ser Ile Leu Asn Leu Pro Gly Glu Ser Thr Leu Arg Arg 340 345 350 Asp Phe Leu Arg Leu Gln Leu Ala Asn Lys Glu Arg Ser Glu Ala Leu 355 360 365 Arg Arg Gln Gln Leu Glu Gln Gln Gln Arg Glu Asn Glu Glu His Lys 370 375 380 Arg Gln Leu Leu Ala Glu Arg Gln Lys Arg Ile Glu Glu Gln Lys Glu 385 390 395 400 Gln Arg Arg Arg Leu Glu Glu Gln Gln Arg Arg Glu Lys Glu Leu Arg 405 410 415 Lys Gln Gln Glu Arg Glu Gln Arg Arg His Tyr Glu Glu Gln Met Arg 420 425 430 Arg Glu Glu Glu Arg Arg Arg Ala Glu His Glu Gln Glu Tyr Lys Arg 435 440 445 Lys Gln Leu Glu Glu Gln Arg Gln Ala Glu Arg Leu Gln Arg Gln Leu 450 455 460 Lys Gln Glu Arg Asp Tyr Leu Val Ser Leu Gln His Gln Arg Gln Glu 465 470 475 480 Gln Arg Pro Val Glu Lys Lys Pro Leu Tyr His Tyr Lys Glu Gly Met 485 490 495 Ser Pro Ser Glu Lys Pro Ala Trp Ala Lys Glu Ile Pro His Leu Val 500 505 510 Ala Val Lys Ser Gln Gly Pro Ala Leu Thr Ala Ser Gln Ser Val His 515 520 525 Glu Gln Pro Thr Lys Gly Leu Ser Gly Phe Gln Glu Ala Leu Asn Val 530 535 540 Thr Ser His Arg Val Glu Met Pro Arg Gln Asn Ser Asp Pro Thr Ser 545 550 555 560 Glu Asn Pro Pro Leu Pro Thr Arg Ile Glu Lys Phe Asp Arg Ser Ser 565 570 575 Trp Leu Arg Gln Glu Glu Asp Ile Pro Pro Lys Val Pro Gln Arg Thr 580 585 590 Thr Ser Ile Ser Pro Ala Leu Ala Arg Lys Asn Ser Pro Gly Asn Gly 595 600 605 Ser Ala Leu Gly Pro Arg Leu Gly Ser Gln Pro Ile Arg Ala Ser Asn 610 615 620 Pro Asp Leu Arg Arg Thr Glu Pro Ile Leu Glu Ser Pro Leu Gln Arg 625 630 635 640 Thr Ser Ser Gly Ser Ser Ser Ser Ser Ser Thr Pro Ser Ser Gln Pro 645 650 655 Ser Ser Gln Gly Gly Ser Gln Pro Gly Ser Gln Ala Gly Ser Ser Glu 660 665 670 Arg Thr Arg Val Arg Ala Asn Ser Lys Ser Glu Gly Ser Pro Val Leu 675 680 685 Pro His Glu Pro Ala Lys Val Lys Pro Glu Glu Ser Arg Asp Ile Thr 690 695 700 Arg Pro Ser Arg Pro Ala Asp Leu Thr Ala Leu Ala Lys Glu Leu Arg 705 710 715 720 Glu Leu Arg Ile Glu Glu Thr Asn Arg Pro Met Lys Lys Val Thr Asp 725 730 735 Tyr Ser Ser Ser Ser Glu Glu Ser Glu Ser Ser Glu Glu Glu Glu Glu 740 745 750 Asp Gly Glu Ser Glu Thr His Asp Gly Thr Val Ala Val Ser Asp Ile 755 760 765 Pro Arg Leu Ile Pro Thr Gly Ala Pro Gly Ser Asn Glu Gln Tyr Asn 770 775 780 Val Gly Met Val Gly Thr His Gly Leu Glu Thr Ser His Ala Asp Ser 785 790 795 800 Phe Ser Gly Ser Ile Ser Arg Glu Gly Thr Leu Met Ile Arg Glu Thr 805 810 815 Ser Gly Glu Lys Lys Arg Ser Gly His Ser Asp Ser Asn Gly Phe Ala 820 825 830 Gly His Ile Asn Leu Pro Asp Leu Val Gln Gln Ser His Ser Pro Ala 835 840 845 Gly Thr Pro Thr Glu Gly Leu Gly Arg Val Ser Thr His Ser Gln Glu 850 855 860 Met Asp Ser Gly Thr Glu Tyr Gly Met Gly Ser Ser Thr Lys Ala Ser 865 870 875 880 Phe Thr Pro Phe Val Asp Pro Arg Val Tyr Gln Thr Ser Pro Thr Asp 885 890 895 Glu Asp Glu Glu Asp Glu Glu Ser Ser Ala Ala Ala Leu Phe Thr Ser 900 905 910 Glu Leu Leu Arg Gln Glu Gln Ala Lys Leu Asn Glu Ala Arg Lys Ile 915 920 925 Ser Val Val Asn Val Asn Pro Thr Asn Ile Arg Pro His Ser Asp Thr 930 935 940 Pro Glu Ile Arg Lys Tyr Lys Lys Arg Phe Asn Ser Glu Ile Leu Cys 945 950 955 960 Ala Ala Leu Trp Gly Val Asn Leu Leu Val Gly Thr Glu Asn Gly Leu 965 970 975 Met Leu Leu Asp Arg Ser Gly Gln Gly Lys Val Tyr Asn Leu Ile Asn 980 985 990 Arg Arg Arg Phe Gln Gln Met Asp Val Leu Glu Gly Leu Asn Val Leu 995 1000 1005 Val Thr Ile Ser Gly Lys Lys Asn Lys Leu Arg Val Tyr Tyr Leu Ser 1010 1015 1020 Trp Leu Arg Asn Arg Ile Leu His Asn Asp Pro Glu Val Glu Lys Lys 1025 1030 1035 1040 Gln Gly Trp Ile Thr Val Gly Asp Leu Glu Gly Cys Ile His Tyr Lys 1045 1050 1055 Val Val Lys Tyr Glu Arg Ile Lys Phe Leu Val Ile Ala Leu Lys Asn 1060 1065 1070 Ala Val Glu Ile Tyr Ala Trp Ala Pro Lys Pro Tyr His Lys Phe Met 1075 1080 1085 Ala Phe Lys Ser Phe Ala Asp Leu Gln His Lys Pro Leu Leu Val Asp 1090 1095 1100 Leu Thr Val Glu Glu Gly Gln Arg Leu Lys Val Ile Phe Gly Ser His 1105 1110 1115 1120 Thr Gly Phe His Val Ile Asp Val Asp Ser Gly Asn Ser Tyr Asp Ile 1125 1130 1135 Tyr Ile Pro Ser His Ile Gln Gly Asn Ile Thr Pro His Ala Ile Val 1140 1145 1150 Ile Leu Pro Lys Thr Asp Gly Met Glu Met Leu Val Cys Tyr Glu Asp 1155 1160 1165 Glu Gly Val Tyr Val Asn Thr Tyr Gly Arg Ile Thr Lys Asp Val Val 1170 1175 1180 Leu Gln Trp Gly Glu Met Pro Thr Ser Val Ala Tyr Ile His Ser Asn 1185 1190 1195 1200 Gln Ile Met Gly Trp Gly Glu Lys Ala Ile Glu Ile Arg Ser Val Glu 1205 1210 1215 Thr Gly His Leu Asp Gly Val Phe Met His Lys Arg Ala Gln Arg Leu 1220 1225 1230 Lys Phe Leu Cys Glu Arg Asn Asp Lys Val Phe Phe Ala Ser Val Arg 1235 1240 1245 Ser Gly Gly Ser Ser Gln Val Phe Phe Met Thr Leu Asn Arg Asn Ser 1250 1255 1260 Met Met Asn Trp 1265 123 2354 DNA Homo Sapiens 123 gggaggaccc caatctaggc ccaagaggga aaggccacgt gcctgtatga gcgtatgagc 60 atgtgcatgc gcgtgtgtgc acagggtggt gcacctggca ggggtccttg agtgaggcat 120 gccccattct gtagcaggga acctggaatg ggctgtgtgt tctgcaagaa attggagccg 180 gtggccacgg ccaaggagga tgctggcctg gaaggggact tcagaagcta cggggcagca 240 gaccactatg ggcctgaccc cactaaggcc cggcctgcat cctcatttgc ccacatcccc 300 aactacagca acttctcctc tcaggccatc aaccctggct tccttgatag tggcaccatc 360 aggggtgtgt cagggattgg ggtgaccctg ttcattgccc tgtatgacta tgaggctcga 420 actgaggatg acctcacctt caccaagggc gagaagttcc acatcctgaa caatactgaa 480 ggtgactggt gggaggctcg gtctctcagc tccggaaaaa ctggctgcat tcccagcaac 540 tacgtggccc ctgttgactc aatccaagct gaagagtggt actttggaaa gattgggaga 600 aaggatgcag agaggcagct gctttcacca ggcaaccccc agggggcctt tctcattcgg 660 gaaagcgaga ccaccaaagg tgcctactcc ctgtccatcc gggactggga tcagaccaga 720 ggcgatcatg tgaagcatta caagatccgc aaactggaca tgggcggcta ctacatcacc 780 acacgggttc agttcaactc ggtgcaggag ctggtgcagc actacatgga ggtgaatgac 840 gggctgtgca acctgctcat cgcgccctgc accatcatga agccgcagac gctgggcctg 900 gccaaggacg cctgggagat cagccgcagc tccatcacgc tggagcgccg gctgggcacc 960 ggctgcttcg gggatgtgtg gctgggcacg tggaacggca gcactaaggt ggcggtgaag 1020 acgctgaagc cgggcaccat gtccccgaag gccttcctgg aggaggcgca ggtcatgaag 1080 ctgctgcggc acgacaagct ggtgcagctg tacgccgtgg tgtcggagga gcccatctac 1140 atcgtgaccg agttcatgtg tcacggcagc ttgctggatt ttctcaagaa cccagagggc 1200 caggatttga ggctgcccca attggtggac atggcagccc aggtagctga gggcatggcc 1260 tacatggaac gcatgaacta cattcaccgc gacctgaggg cagccaacat cctggttggg 1320 gagcggctgg cgtgcaagat cgcagacttt ggcttggcgc gtctcatcaa ggacgatgag 1380 tacaacccct gccaaggttc caagttcccc atcaagtgga cagccccaga agctgccctc 1440 tttggcagat tcaccatcaa gtcagacgtg tggtcctttg ggatcctgct cactgagctc 1500 atcaccaagg gccgaatccc ctacccaggc atgaataaac gggaagtgtt ggaacaggtg 1560 gagcagggct accacatgcc gtgccctcca ggctgcccag catccctgta cgaggccatg 1620 gaacagacct ggcgtctgga cccggaggag aggcctacct tcgagtacct gcagtccttc 1680 ctggaggact acttcacctc cgctgaacca cagtaccagc ccggggatca gacatagcct 1740 gtccgggcat caaccctctc tggcggtggc caccagtcct tgccaatccc cagagctgtt 1800 cttccaaagc ccccaggctg gcttagaacc ccatagagtc ctagcatcac cgaggacgtg 1860 gctgctctga caccacctag ggcaacctac ttgttttaca gatggggcaa aaggaggccc 1920 agagctgatc tctcatccgc tctggcccca agcactattt cttccttttc cacttaggcc 1980 cctacatgcc tgtagccctt tctcactcca tccccaccca aaagtgctca gaccttgtct 2040 agttatttat aaactgtatg tacctccctc acttctctcc tatcactgct ttcctactct 2100 ccttttatct cactctagtc caggtgccaa gaatttccct tctaccctct attctcttgt 2160 gtctgtaagt tacaaagtca ggaaaagtct tggctggacc cctttcctgc tgggtggatg 2220 cagtggtcca ggactggggt ctgggcccag gtttgaggga gaagtttgca gagcacttcc 2280 cacctctctg aatagtgtgt atgtgttgat ttattgattc tgtaaataag taaaatgaca 2340 atatgaatcc tcca 2354 124 529 PRT Homo Sapiens 124 Met Gly Cys Val Phe Cys Lys Lys Leu Glu Pro Val Ala Thr Ala Lys 1 5 10 15 Glu Asp Ala Gly Leu Glu Gly Asp Phe Arg Ser Tyr Gly Ala Ala Asp 20 25 30 His Tyr Gly Pro Asp Pro Thr Lys Ala Arg Pro Ala Ser Ser Phe Ala 35 40 45 His Ile Pro Asn Tyr Ser Asn Phe Ser Ser Gln Ala Ile Asn Pro Gly 50 55 60 Phe Leu Asp Ser Gly Thr Ile Arg Gly Val Ser Gly Ile Gly Val Thr 65 70 75 80 Leu Phe Ile Ala Leu Tyr Asp Tyr Glu Ala Arg Thr Glu Asp Asp Leu 85 90 95 Thr Phe Thr Lys Gly Glu Lys Phe His Ile Leu Asn Asn Thr Glu Gly 100 105 110 Asp Trp Trp Glu Ala Arg Ser Leu Ser Ser Gly Lys Thr Gly Cys Ile 115 120 125 Pro Ser Asn Tyr Val Ala Pro Val Asp Ser Ile Gln Ala Glu Glu Trp 130 135 140 Tyr Phe Gly Lys Ile Gly Arg Lys Asp Ala Glu Arg Gln Leu Leu Ser 145 150 155 160 Pro Gly Asn Pro Gln Gly Ala Phe Leu Ile Arg Glu Ser Glu Thr Thr 165 170 175 Lys Gly Ala Tyr Ser Leu Ser Ile Arg Asp Trp Asp Gln Thr Arg Gly 180 185 190 Asp His Val Lys His Tyr Lys Ile Arg Lys Leu Asp Met Gly Gly Tyr 195 200 205 Tyr Ile Thr Thr Arg Val Gln Phe Asn Ser Val Gln Glu Leu Val Gln 210 215 220 His Tyr Met Glu Val Asn Asp Gly Leu Cys Asn Leu Leu Ile Ala Pro 225 230 235 240 Cys Thr Ile Met Lys Pro Gln Thr Leu Gly Leu Ala Lys Asp Ala Trp 245 250 255 Glu Ile Ser Arg Ser Ser Ile Thr Leu Glu Arg Arg Leu Gly Thr Gly 260 265 270 Cys Phe Gly Asp Val Trp Leu Gly Thr Trp Asn Gly Ser Thr Lys Val 275 280 285 Ala Val Lys Thr Leu Lys Pro Gly Thr Met Ser Pro Lys Ala Phe Leu 290 295 300 Glu Glu Ala Gln Val Met Lys Leu Leu Arg His Asp Lys Leu Val Gln 305 310 315 320 Leu Tyr Ala Val Val Ser Glu Glu Pro Ile Tyr Ile Val Thr Glu Phe 325 330 335 Met Cys His Gly Ser Leu Leu Asp Phe Leu Lys Asn Pro Glu Gly Gln 340 345 350 Asp Leu Arg Leu Pro Gln Leu Val Asp Met Ala Ala Gln Val Ala Glu 355 360 365 Gly Met Ala Tyr Met Glu Arg Met Asn Tyr Ile His Arg Asp Leu Arg 370 375 380 Ala Ala Asn Ile Leu Val Gly Glu Arg Leu Ala Cys Lys Ile Ala Asp 385 390 395 400 Phe Gly Leu Ala Arg Leu Ile Lys Asp Asp Glu Tyr Asn Pro Cys Gln 405 410 415 Gly Ser Lys Phe Pro Ile Lys Trp Thr Ala Pro Glu Ala Ala Leu Phe 420 425 430 Gly Arg Phe Thr Ile Lys Ser Asp Val Trp Ser Phe Gly Ile Leu Leu 435 440 445 Thr Glu Leu Ile Thr Lys Gly Arg Ile Pro Tyr Pro Gly Met Asn Lys 450 455 460 Arg Glu Val Leu Glu Gln Val Glu Gln Gly Tyr His Met Pro Cys Pro 465 470 475 480 Pro Gly Cys Pro Ala Ser Leu Tyr Glu Ala Met Glu Gln Thr Trp Arg 485 490 495 Leu Asp Pro Glu Glu Arg Pro Thr Phe Glu Tyr Leu Gln Ser Phe Leu 500 505 510 Glu Asp Tyr Phe Thr Ser Ala Glu Pro Gln Tyr Gln Pro Gly Asp Gln 515 520 525 Thr 125 2374 DNA Homo Sapiens 125 aggcggcaga gaggagacta tggaacgtca ggtgctgctg agcgagcccg aggaggcggc 60 ggctctgtat cggggcctta gccgccagcc cgcgctgagc gccgcctgcc tgggcccgga 120 ggtcaccaca cagtacggcg gccagtaccg gacggtgcac actgagtgga cccagaggga 180 cctggaacgc atggagaaca ttcgattctg ccgccaatac ctggtgttcc atgacgggga 240 ctcagtggtg tttgccggac ctgcaggcaa cagtgtggag acccgggggg aactgctgag 300 cagagagtct ccttcaggca gcatgaaagc tgtgctgcgc aaggctggag gcacgggccc 360 tggggaagag aagcagttcc tggaggtctg ggagaagaac cggaagctca agagtttcaa 420 cctatcagtg ctggagaaac atgggcctgt ttatgaggat gactgttttg gctgcctgtc 480 ctggtcgcac tcggagacac acttgttgta tgtggcagag aggaagcgcc ccaaggccga 540 gtccttcttt cagaccaaag ccttggacgt cagtgccagc gatgatgaga tagccaggct 600 gaagaagcca gaccaaccca tcaaggggga tcagtttgtg ttttacgaag actggggaga 660 aaacatggtt tccaaaagca tccctgtgct ctgcgtgctg gatgtcgaga gtggcaacat 720 ctctgtgctt gagggggtcc ctgagaatgt gtcccctgga caggcatttt gggcccctgg 780 agatgctggt gtggtgtttg tgggctggtg gcatgagccc ttccggttgg gcatccgctt 840 ttgcaccaat cgcaggtcag ccctgtatta tgtggacctc atcgggggga agtgtgagct 900 cctctcggat gactccctgg ctgtctcttc tccccggctg agcccagacc aatgtcgcat 960 tgtctacctg cagtacccat ctctgatccc ccatcaccaa tgcagccagc tgtgcctgta 1020 tgactggtat accaaggtta cctcagtggt ggtagatgtt gtgcctcggc agctgggaga 1080 gaacttctct gggatctact gcagccttct gcctttggga tgctggtcag ctgacagcca 1140 gagagtggtc tttgactcgg ctcagcgcag ccggcaggac ctgtttgctg tggacaccca 1200 agtgggcact gtgacctccc tcacagctgg agggtcaggt gggagctgga agttgctcac 1260 aattgaccag gacctcatgg tggcacagtt ttccacaccc agcctacctc caaccctgaa 1320 agttgggttc ctgccttctg cagggaagga gcagtcagtg ttgtgggtgt ccctggagga 1380 ggccgagccc attcccgaca tccactgggg catccgggtg ctacagccac ccccagagca 1440 agagaatgtg cagtatgctg gccttgactt tgaagcaatc ctgctgcagc ctggcagccc 1500 tccagataag acccaagtgc ccatggtggt catgccccac ggggggcccc attcatcctt 1560 tgtcactgcc tggatgctgt tcccagccat gctttgcaag atgggctttg cggtactact 1620 agtgaactat cgtggctcca cgggctttgg ccaggacagc atcctctccc tcccaggcaa 1680 tgtgggccac caggatgtga aggatgtcca gtttgcagtg gaacaggtgc tccaggagga 1740 acactttgat gcaagccatg tggcccttat gggtggttcc catggtggct tcatttcctg 1800 ccacttgatt ggtcagtacc cagagaccta cagggcctgc gtggcccgga accccgtgat 1860 caacatcgcc tccatgttgg gctccactga catccctgac tggtgcgtgg tggaggctgg 1920 ctttcctttc agcagtgact gcctgccaga cctcagcgtg tgggctgaga tgctggacaa 1980 atcgcccatc agatacatcc ctcaggtgaa gacaccactg ttactgatgt tgggccagga 2040 ggaccggcgt gtgcccttca agcagggcat ggagtattac cgtgccctca agacccggaa 2100 tgtgcctgtt cggctcctgc tctatcccaa aagcacccac gcattatcag aggtggaggt 2160 ggagtcagac agcttcatga atgctgtgct ctggctacgc acacacttgg gcagctgaag 2220 ccctgccatt ctgcatgagc tgatcagcct gtgccacact tcgctcttga ggagctcaac 2280 ggtctggcag ggcagcagga ggctttctgg gctctggact ccacggatgc gtgggcagag 2340 gaatgtgggc tatgtagtca taataaatta ggac 2374 126 732 PRT Homo Sapiens 126 Met Glu Arg Gln Val Leu Leu Ser Glu Pro Glu Glu Ala Ala Ala Leu 1 5 10 15 Tyr Arg Gly Leu Ser Arg Gln Pro Ala Leu Ser Ala Ala Cys Leu Gly 20 25 30 Pro Glu Val Thr Thr Gln Tyr Gly Gly Gln Tyr Arg Thr Val His Thr 35 40 45 Glu Trp Thr Gln Arg Asp Leu Glu Arg Met Glu Asn Ile Arg Phe Cys 50 55 60 Arg Gln Tyr Leu Val Phe His Asp Gly Asp Ser Val Val Phe Ala Gly 65 70 75 80 Pro Ala Gly Asn Ser Val Glu Thr Arg Gly Glu Leu Leu Ser Arg Glu 85 90 95 Ser Pro Ser Gly Ser Met Lys Ala Val Leu Arg Lys Ala Gly Gly Thr 100 105 110 Gly Pro Gly Glu Glu Lys Gln Phe Leu Glu Val Trp Glu Lys Asn Arg 115 120 125 Lys Leu Lys Ser Phe Asn Leu Ser Val Leu Glu Lys His Gly Pro Val 130 135 140 Tyr Glu Asp Asp Cys Phe Gly Cys Leu Ser Trp Ser His Ser Glu Thr 145 150 155 160 His Leu Leu Tyr Val Ala Glu Arg Lys Arg Pro Lys Ala Glu Ser Phe 165 170 175 Phe Gln Thr Lys Ala Leu Asp Val Ser Ala Ser Asp Asp Glu Ile Ala 180 185 190 Arg Leu Lys Lys Pro Asp Gln Pro Ile Lys Gly Asp Gln Phe Val Phe 195 200 205 Tyr Glu Asp Trp Gly Glu Asn Met Val Ser Lys Ser Ile Pro Val Leu 210 215 220 Cys Val Leu Asp Val Glu Ser Gly Asn Ile Ser Val Leu Glu Gly Val 225 230 235 240 Pro Glu Asn Val Ser Pro Gly Gln Ala Phe Trp Ala Pro Gly Asp Ala 245 250 255 Gly Val Val Phe Val Gly Trp Trp His Glu Pro Phe Arg Leu Gly Ile 260 265 270 Arg Phe Cys Thr Asn Arg Arg Ser Ala Leu Tyr Tyr Val Asp Leu Ile 275 280 285 Gly Gly Lys Cys Glu Leu Leu Ser Asp Asp Ser Leu Ala Val Ser Ser 290 295 300 Pro Arg Leu Ser Pro Asp Gln Cys Arg Ile Val Tyr Leu Gln Tyr Pro 305 310 315 320 Ser Leu Ile Pro His His Gln Cys Ser Gln Leu Cys Leu Tyr Asp Trp 325 330 335 Tyr Thr Lys Val Thr Ser Val Val Val Asp Val Val Pro Arg Gln Leu 340 345 350 Gly Glu Asn Phe Ser Gly Ile Tyr Cys Ser Leu Leu Pro Leu Gly Cys 355 360 365 Trp Ser Ala Asp Ser Gln Arg Val Val Phe Asp Ser Ala Gln Arg Ser 370 375 380 Arg Gln Asp Leu Phe Ala Val Asp Thr Gln Val Gly Thr Val Thr Ser 385 390 395 400 Leu Thr Ala Gly Gly Ser Gly Gly Ser Trp Lys Leu Leu Thr Ile Asp 405 410 415 Gln Asp Leu Met Val Ala Gln Phe Ser Thr Pro Ser Leu Pro Pro Thr 420 425 430 Leu Lys Val Gly Phe Leu Pro Ser Ala Gly Lys Glu Gln Ser Val Leu 435 440 445 Trp Val Ser Leu Glu Glu Ala Glu Pro Ile Pro Asp Ile His Trp Gly 450 455 460 Ile Arg Val Leu Gln Pro Pro Pro Glu Gln Glu Asn Val Gln Tyr Ala 465 470 475 480 Gly Leu Asp Phe Glu Ala Ile Leu Leu Gln Pro Gly Ser Pro Pro Asp 485 490 495 Lys Thr Gln Val Pro Met Val Val Met Pro His Gly Gly Pro His Ser 500 505 510 Ser Phe Val Thr Ala Trp Met Leu Phe Pro Ala Met Leu Cys Lys Met 515 520 525 Gly Phe Ala Val Leu Leu Val Asn Tyr Arg Gly Ser Thr Gly Phe Gly 530 535 540 Gln Asp Ser Ile Leu Ser Leu Pro Gly Asn Val Gly His Gln Asp Val 545 550 555 560 Lys Asp Val Gln Phe Ala Val Glu Gln Val Leu Gln Glu Glu His Phe 565 570 575 Asp Ala Ser His Val Ala Leu Met Gly Gly Ser His Gly Gly Phe Ile 580 585 590 Ser Cys His Leu Ile Gly Gln Tyr Pro Glu Thr Tyr Arg Ala Cys Val 595 600 605 Ala Arg Asn Pro Val Ile Asn Ile Ala Ser Met Leu Gly Ser Thr Asp 610 615 620 Ile Pro Asp Trp Cys Val Val Glu Ala Gly Phe Pro Phe Ser Ser Asp 625 630 635 640 Cys Leu Pro Asp Leu Ser Val Trp Ala Glu Met Leu Asp Lys Ser Pro 645 650 655 Ile Arg Tyr Ile Pro Gln Val Lys Thr Pro Leu Leu Leu Met Leu Gly 660 665 670 Gln Glu Asp Arg Arg Val Pro Phe Lys Gln Gly Met Glu Tyr Tyr Arg 675 680 685 Ala Leu Lys Thr Arg Asn Val Pro Val Arg Leu Leu Leu Tyr Pro Lys 690 695 700 Ser Thr His Ala Leu Ser Glu Val Glu Val Glu Ser Asp Ser Phe Met 705 710 715 720 Asn Ala Val Leu Trp Leu Arg Thr His Leu Gly Ser 725 730 

What is claimed:
 1. A method for identifying a compound capable of treating a cardiovascular disorder, comprising assaying the ability of the compound to modulate 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid expression or 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide activity, thereby identifying a compound capable of treating a cardiovascular disorder.
 2. A method for identifying a compound capable of modulating lipid production comprising: a) contacting a cell which expresses 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 with a test compound; and b) assaying the ability of the test compound to modulate the expression of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid, or the activity of a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide, thereby identifying a compound capable of modulating lipid production.
 3. A method for modulating lipid production in a cell comprising contacting a cell with a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator, thereby modulating lipid production in the cell.
 4. The method of claim 2, wherein the cell is a hepatic cell.
 5. The method of claim 3, wherein the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator is a small organic molecule, peptide, antibody or antisense nucleic acid molecule.
 6. The method of claim 3, wherein the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator is capable of modulating 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide activity.
 7. The method of claim 6, wherein the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator is a small organic molecule, peptide, antibody or antisense nucleic acid molecule.
 8. The method of claim 6, wherein the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator is capable of modulating 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid expression.
 9. A method for treating a subject having a cardiovascular disorder characterized by aberrant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide activity or aberrant 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 nucleic acid expression comprising administering to the subject a 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator, thereby treating said subject having a cardiovascular disorder.
 10. The method of claim 9, wherein said cardiovascular disorder is selected from the group consisting of arteriosclerosis, atherosclerosis, cardiac hypertrophy, ischemia reperfusion injury, restenosis, arterial inflammation, vascular wall remodeling, ventricular remodeling, rapid ventricular pacing, coronary microembolism, tachycardia, bradycardia, pressure overload, aortic bending, coronary artery ligation, vascular heart disease, valvular disease, including but not limited to, valvular degeneration caused by calcification, rheumatic heart disease, endocarditis, or complications of artificial valves; atrial fibrillation, long-QT syndrome, congestive heart failure, sinus node dysfunction, angina, heart failure, hypertension, atrial fibrillation, atrial flutter, pericardial disease, including but not limited to, pericardial effusion and pericarditis; cardiomyopathies, e.g., dilated cardiomyopathy or idiopathic cardiomyopathy, myocardial infarction, coronary artery disease, coronary artery spasm, ischemic disease, arrhythmia, sudden cardiac death, and cardiovascular developmental disorders
 11. The method of claim 9, wherein said 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator is administered in a pharmaceutically acceptable formulation.
 12. The method of claim 9, wherein the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator is a small organic molecule, peptide, antibody or antisense nucleic acid molecule.
 13. The method of claim 9, wherein the 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 modulator is capable of modulating 1682, 6169, 6193, 7771, 14395, 29002, 33216, 43726, 69292, 21656, 32427, 2402, 7747, 1720, 9151, 60491, 1371, 7077, 33207, 1419, 18036, 16105, 38650, 14245, 58848, 1870, 25856, 32394, 3484, 345, 9252, 9135, 10532, 18610, 8165, 2448, 2445, 64624, 84237, 8912, 2868, 283, 2554, 9464, 17799, 26686, 43848, 32135, 12208, 2914, 51130, 19489, 21833, 2917, 59590, 15992, 2094, 2252, 3474, 9792, 15400, 1452 or 6585 polypeptide activity. 